Sample records for abnormal neural responses

  1. Abnormal cardiovascular response to exercise in hypertension: contribution of neural factors.

    PubMed

    Mitchell, Jere H

    2017-06-01

    During both dynamic (e.g., endurance) and static (e.g., strength) exercise there are exaggerated cardiovascular responses in hypertension. This includes greater increases in blood pressure, heart rate, and efferent sympathetic nerve activity than in normal controls. Two of the known neural factors that contribute to this abnormal cardiovascular response are the exercise pressor reflex (EPR) and functional sympatholysis. The EPR originates in contracting skeletal muscle and reflexly increases sympathetic efferent nerve activity to the heart and blood vessels as well as decreases parasympathetic efferent nerve activity to the heart. These changes in autonomic nerve activity cause an increase in blood pressure, heart rate, left ventricular contractility, and vasoconstriction in the arterial tree. However, arterial vessels in the contracting skeletal muscle have a markedly diminished vasoconstrictor response. The markedly diminished vasoconstriction in contracting skeletal muscle has been termed functional sympatholysis. It has been shown in hypertension that there is an enhanced EPR, including both its mechanoreflex and metaboreflex components, and an impaired functional sympatholysis. These conditions set up a positive feedback or vicious cycle situation that causes a progressively greater decrease in the blood flow to the exercising muscle. Thus these two neural mechanisms contribute significantly to the abnormal cardiovascular response to exercise in hypertension. In addition, exercise training in hypertension decreases the enhanced EPR, including both mechanoreflex and metaboreflex function, and improves the impaired functional sympatholysis. These two changes, caused by exercise training, improve the muscle blood flow to exercising muscle and cause a more normal cardiovascular response to exercise in hypertension. Copyright © 2017 the American Physiological Society.

  2. Detection of Structural Abnormalities Using Neural Nets

    NASA Technical Reports Server (NTRS)

    Zak, M.; Maccalla, A.; Daggumati, V.; Gulati, S.; Toomarian, N.

    1996-01-01

    This paper describes a feed-forward neural net approach for detection of abnormal system behavior based upon sensor data analyses. A new dynamical invariant representing structural parameters of the system is introduced in such a way that any structural abnormalities in the system behavior are detected from the corresponding changes to the invariant.

  3. [Tilt test and orthostatic intolerance: abnormalities in the neural sympathetic response to gravitational stimulus].

    PubMed

    Furlan, R

    2001-05-01

    In the present manuscript the different methodologies aimed at assessing the autonomic profile in humans during a gravitational stimulus have been described. In addition, strengths and drawbacks of the tilt test in relation to occasional orthostatic intolerance were addressed. Finally, different autonomic abnormalities underlying occasional and chronic orthostatic intolerance syndromes have been schematically highlighted. The direct recording of the neural sympathetic discharge from the peroneal nerve (MSNA), in spite of its invasive nature, still represents the recognized reference to quantify the changes in the sympathetic activity to the vessels attending postural modifications. The increase of plasma norepinephrine during a tilt test is achieved by both an increase in plasma spillover and a concomitant decrease in systemic clearance. Changes in the indices of cardiac sympathetic and vagal modulation may also be quantified during a tilt test by power spectrum analysis of RR interval variability. The spectral markers of cardiac autonomic control, if evaluated concomitantly with MSNA, may contribute to assess abnormalities in the regional distribution of the sympathetic activity to the heart and the vessels. The capability of the tilt test of reproducing a vasovagal event or of inducing "false positive responses" seems to be markedly affected by the age, thus suggesting that additional or different etiopathogenetic mechanisms might be involved in the loss of consciousness in older as compared to younger subjects. In subjects suffering from occasional or habitual neurally mediated syncope an increase or, respectively, a decrease in cardiac and vascular sympathetic modulation has been documented before the loss of consciousness. In patients with pure autonomic failure, a global dysautonomia affecting both the sympathetic and the vagal modulation to the heart, seems to be present. In chronic orthostatic intolerance, the most common form of dysautonomia of young women

  4. Abnormal neural hierarchy in processing of verbal information in patients with schizophrenia.

    PubMed

    Lerner, Yulia; Bleich-Cohen, Maya; Solnik-Knirsh, Shimrit; Yogev-Seligmann, Galit; Eisenstein, Tamir; Madah, Waheed; Shamir, Alon; Hendler, Talma; Kremer, Ilana

    2018-01-01

    Previous research indicates abnormal comprehension of verbal information in patients with schizophrenia. Yet the neural mechanism underlying the breakdown of verbal information processing in schizophrenia is poorly understood. Imaging studies in healthy populations have shown a network of brain areas involved in hierarchical processing of verbal information over time. Here, we identified critical aspects of this hierarchy, examining patients with schizophrenia. Using functional magnetic resonance imaging, we examined various levels of information comprehension elicited by naturally presented verbal stimuli; from a set of randomly shuffled words to an intact story. Specifically, patients with first episode schizophrenia ( N  = 15), their non-manifesting siblings ( N  = 14) and healthy controls ( N  = 15) listened to a narrated story and randomly scrambled versions of it. To quantify the degree of dissimilarity between the groups, we adopted an inter-subject correlation (inter-SC) approach, which estimates differences in synchronization of neural responses within and between groups. The temporal topography found in healthy and siblings groups were consistent with our previous findings - high synchronization in responses from early sensory toward high order perceptual and cognitive areas. In patients with schizophrenia, stimuli with short and intermediate temporal scales evoked a typical pattern of reliable responses, whereas story condition (long temporal scale) revealed robust and widespread disruption of the inter-SCs. In addition, the more similar the neural activity of patients with schizophrenia was to the average response in the healthy group, the less severe the positive symptoms of the patients. Our findings suggest that system-level neural indication of abnormal verbal information processing in schizophrenia reflects disease manifestations.

  5. Artificial Neural Network for the Prediction of Chromosomal Abnormalities in Azoospermic Males.

    PubMed

    Akinsal, Emre Can; Haznedar, Bulent; Baydilli, Numan; Kalinli, Adem; Ozturk, Ahmet; Ekmekçioğlu, Oğuz

    2018-02-04

    To evaluate whether an artifical neural network helps to diagnose any chromosomal abnormalities in azoospermic males. The data of azoospermic males attending to a tertiary academic referral center were evaluated retrospectively. Height, total testicular volume, follicle stimulating hormone, luteinising hormone, total testosterone and ejaculate volume of the patients were used for the analyses. In artificial neural network, the data of 310 azoospermics were used as the education and 115 as the test set. Logistic regression analyses and discriminant analyses were performed for statistical analyses. The tests were re-analysed with a neural network. Both logistic regression analyses and artificial neural network predicted the presence or absence of chromosomal abnormalities with more than 95% accuracy. The use of artificial neural network model has yielded satisfactory results in terms of distinguishing patients whether they have any chromosomal abnormality or not.

  6. Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome.

    PubMed

    Walton, Mark M G; Pallus, Adam; Fleuriet, Jérome; Mustari, Michael J; Tarczy-Hornoch, Kristina

    2017-07-01

    Infantile strabismus is characterized by numerous visual and oculomotor abnormalities. Recently nonhuman primate models of infantile strabismus have been established, with characteristics that closely match those observed in human patients. This has made it possible to study the neural basis for visual and oculomotor symptoms in infantile strabismus. In this review, we consider the available evidence for neural abnormalities in structures related to oculomotor pathways ranging from visual cortex to oculomotor nuclei. These studies provide compelling evidence that a disturbance of binocular vision during a sensitive period early in life, whatever the cause, results in a cascade of abnormalities through numerous brain areas involved in visual functions and eye movements. Copyright © 2017 the American Physiological Society.

  7. 5-Mehtyltetrahydrofolate rescues alcohol-induced neural crest cell migration abnormalities.

    PubMed

    Shi, Yu; Li, Jiejing; Chen, Chunjiang; Gong, Manzi; Chen, Yuan; Liu, Youxue; Chen, Jie; Li, Tingyu; Song, Weihong

    2014-09-16

    Alcohol is detrimental to early development. Fetal alcohol spectrum disorders (FASD) due to maternal alcohol abuse results in a series of developmental abnormalities including cranial facial dysmorphology, ocular anomalies, congenital heart defects, microcephaly and intellectual disabilities. Previous studies have been shown that ethanol exposure causes neural crest (NC) apoptosis and perturbation of neural crest migration. However, the underlying mechanism remains elusive. In this report we investigated the fetal effect of alcohol on the process of neural crest development in the Xenopus leavis. Pre-gastrulation exposure of 2-4% alcohol induces apoptosis in Xenopus embryo whereas 1% alcohol specifically impairs neural crest migration without observing discernible apoptosis. Additionally, 1% alcohol treatment considerably increased the phenotype of small head (43.4% ± 4.4%, total embryo n = 234), and 1.5% and 2.0% dramatically augment the deformation to 81.2% ± 6.5% (n = 205) and 91.6% ± 3.0% (n = 235), respectively (P < 0.05). Significant accumulation of Homocysteine was caused by alcohol treatment in embryos and 5-mehtyltetrahydrofolate restores neural crest migration and alleviates homocysteine accumulation, resulting in inhibition of the alcohol-induced neurocristopathies. Our study demonstrates that prenatal alcohol exposure causes neural crest cell migration abnormality and 5-mehtyltetrahydrofolate could be beneficial for treating FASD.

  8. Classification of breast abnormalities using artificial neural network

    NASA Astrophysics Data System (ADS)

    Zaman, Nur Atiqah Kamarul; Rahman, Wan Eny Zarina Wan Abdul; Jumaat, Abdul Kadir; Yasiran, Siti Salmah

    2015-05-01

    Classification is the process of recognition, differentiation and categorizing objects into groups. Breast abnormalities are calcifications which are tumor markers that indicate the presence of cancer in the breast. The aims of this research are to classify the types of breast abnormalities using artificial neural network (ANN) classifier and to evaluate the accuracy performance using receiver operating characteristics (ROC) curve. The methods used in this research are ANN for breast abnormalities classifications and Canny edge detector as a feature extraction method. Previously the ANN classifier provides only the number of benign and malignant cases without providing information for specific cases. However in this research, the type of abnormality for each image can be obtained. The existing MIAS MiniMammographic database classified the mammogram images into three features only namely characteristic of background tissues, class of abnormality and radius of abnormality. However, in this research three other features are added-in. These three features are number of spots, area and shape of abnormalities. Lastly the performance of the ANN classifier is evaluated using ROC curve. It is found that ANN has an accuracy of 97.9% which is considered acceptable.

  9. Social anhedonia is associated with neural abnormalities during face emotion processing.

    PubMed

    Germine, Laura T; Garrido, Lucia; Bruce, Lori; Hooker, Christine

    2011-10-01

    Human beings are social organisms with an intrinsic desire to seek and participate in social interactions. Social anhedonia is a personality trait characterized by a reduced desire for social affiliation and reduced pleasure derived from interpersonal interactions. Abnormally high levels of social anhedonia prospectively predict the development of schizophrenia and contribute to poorer outcomes for schizophrenia patients. Despite the strong association between social anhedonia and schizophrenia, the neural mechanisms that underlie individual differences in social anhedonia have not been studied and are thus poorly understood. Deficits in face emotion recognition are related to poorer social outcomes in schizophrenia, and it has been suggested that face emotion recognition deficits may be a behavioral marker for schizophrenia liability. In the current study, we used functional magnetic resonance imaging (fMRI) to see whether there are differences in the brain networks underlying basic face emotion processing in a community sample of individuals low vs. high in social anhedonia. We isolated the neural mechanisms related to face emotion processing by comparing face emotion discrimination with four other baseline conditions (identity discrimination of emotional faces, identity discrimination of neutral faces, object discrimination, and pattern discrimination). Results showed a group (high/low social anhedonia) × condition (emotion discrimination/control condition) interaction in the anterior portion of the rostral medial prefrontal cortex, right superior temporal gyrus, and left somatosensory cortex. As predicted, high (relative to low) social anhedonia participants showed less neural activity in face emotion processing regions during emotion discrimination as compared to each control condition. The findings suggest that social anhedonia is associated with abnormalities in networks responsible for basic processes associated with social cognition, and provide a

  10. Patterns of neural response to emotive stimuli distinguish the different symptom dimensions of obsessive-compulsive disorder.

    PubMed

    Phillips, Mary L; Mataix-Cols, David

    2004-04-01

    Despite its heterogeneous symptomatology, obsessive-compulsive disorder (OCD) is currently conceptualized as a unitary diagnostic entity. Recent factor-analytic studies have identified several OCD symptom dimensions that are associated with different demographic variables, comorbidity, patterns of genetic transmission, and treatment response. Functional abnormalities in neural systems important for emotion perception, including the orbitofrontal cortex, lateral prefrontal cortex, anterior cingulate gyrus, and limbic regions, have been reported in OCD. In this review, we discuss the extent to which neurobiological markers may distinguish these different symptom dimensions and whether specific symptom dimensions, such as contamination/washing, are associated with abnormalities in emotion and, in particular, disgust, perception in OCD. Also discussed are findings that indicate that anxiety can be induced in healthy volunteers in response to OCD symptom-related material, and that associated increases in activity within neural systems important for emotion perception occur to washing- and hoarding-related material in particular in these subjects. Further examination of neural responses during provocation of different symptom dimensions in OCD patients will help determine the extent to which specific abnormalities in neural systems underlying emotion perception are associated with different symptom dimensions and predict treatment response in OCD.

  11. Neural correlates of abnormal sensory discrimination in laryngeal dystonia.

    PubMed

    Termsarasab, Pichet; Ramdhani, Ritesh A; Battistella, Giovanni; Rubien-Thomas, Estee; Choy, Melissa; Farwell, Ian M; Velickovic, Miodrag; Blitzer, Andrew; Frucht, Steven J; Reilly, Richard B; Hutchinson, Michael; Ozelius, Laurie J; Simonyan, Kristina

    2016-01-01

    Aberrant sensory processing plays a fundamental role in the pathophysiology of dystonia; however, its underpinning neural mechanisms in relation to dystonia phenotype and genotype remain unclear. We examined temporal and spatial discrimination thresholds in patients with isolated laryngeal form of dystonia (LD), who exhibited different clinical phenotypes (adductor vs. abductor forms) and potentially different genotypes (sporadic vs. familial forms). We correlated our behavioral findings with the brain gray matter volume and functional activity during resting and symptomatic speech production. We found that temporal but not spatial discrimination was significantly altered across all forms of LD, with higher frequency of abnormalities seen in familial than sporadic patients. Common neural correlates of abnormal temporal discrimination across all forms were found with structural and functional changes in the middle frontal and primary somatosensory cortices. In addition, patients with familial LD had greater cerebellar involvement in processing of altered temporal discrimination, whereas sporadic LD patients had greater recruitment of the putamen and sensorimotor cortex. Based on the clinical phenotype, adductor form-specific correlations between abnormal discrimination and brain changes were found in the frontal cortex, whereas abductor form-specific correlations were observed in the cerebellum and putamen. Our behavioral and neuroimaging findings outline the relationship of abnormal sensory discrimination with the phenotype and genotype of isolated LD, suggesting the presence of potentially divergent pathophysiological pathways underlying different manifestations of this disorder.

  12. Neural conduction abnormality in the brain stem and prevalence of the abnormality in late preterm infants with perinatal problems.

    PubMed

    Jiang, Ze Dong

    2013-08-01

    Neurodevelopment in late preterm infants has recently attracted considerable interest. The prevalence of brain stem conduction abnormality remains unknown. We examined maximum length sequence brain stem auditory evoked response in 163 infants, born at 33-36 weeks gestation, who had various perinatal problems. Compared with 49 normal term infants without problems, the late preterm infants showed a significant increase in III-V and I-V interpeak intervals at all 91-910/s clicks, particularly at 455 and 910/s (p < 0.01-0.001). The I-III interval was slightly increased, without statistically significant difference from the controls at any click rates. These results suggest that neural conduction along the, mainly more central or rostral part of, auditory brain stem is abnormal in late preterm infants with perinatal problems. Of the 163 late preterm infant, the number (and percentage rate) of infants with abnormal I-V interval at 91, 227, 455, and 910/s clicks was, respectively, 11 (6.5%), 17 (10.2%), 37 (22.3%), and 31 (18.7%). The number (and percentage rate) of infants with abnormal III-V interval at these rates was, respectively, 10 (6.0%), 17 (10.2%), 28 (16.9), and 36 (21.2%). Apparently, the abnormal rates were much higher at 455 and 910/s clicks than at lower rates 91 and 227/s. In total, 42 (25.8%) infants showed abnormal I-V and/or III-V intervals. Conduction in, mainly in the more central part, the brain stem is abnormal in late preterm infants with perinatal problems. The abnormality is more detectable at high- than at low-rate sensory stimulation. A quarter of late preterm infants with perinatal problems have brain stem conduction abnormality.

  13. Abnormal Neural Progenitor Cells Differentiated from Induced Pluripotent Stem Cells Partially Mimicked Development of TSC2 Neurological Abnormalities.

    PubMed

    Li, Yaqin; Cao, Jiqing; Chen, Menglong; Li, Jing; Sun, Yiming; Zhang, Yu; Zhu, Yuling; Wang, Liang; Zhang, Cheng

    2017-04-11

    Tuberous sclerosis complex (TSC) is a disease featuring devastating and therapeutically challenging neurological abnormalities. However, there is a lack of specific neural progenitor cell models for TSC. Here, the pathology of TSC was studied using primitive neural stem cells (pNSCs) from a patient presenting a c.1444-2A>C mutation in TSC2. We found that TSC2 pNSCs had higher proliferative activity and increased PAX6 expression compared with those of control pNSCs. Neurons differentiated from TSC2 pNSCs showed enlargement of the soma, perturbed neurite outgrowth, and abnormal connections among cells. TSC2 astrocytes had increased saturation density and higher proliferative activity. Moreover, the activity of the mTOR pathway was enhanced in pNSCs and induced in neurons and astrocytes. Thus, our results suggested that TSC2 heterozygosity caused neurological malformations in pNSCs, indicating that its heterozygosity might be sufficient for the development of neurological abnormalities in patients. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Neural abnormalities in early-onset and adolescence-onset conduct disorder.

    PubMed

    Passamonti, Luca; Fairchild, Graeme; Goodyer, Ian M; Hurford, Georgina; Hagan, Cindy C; Rowe, James B; Calder, Andrew J

    2010-07-01

    Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. Case-control study. Government research institute, university department. Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for

  15. Neural autoantibodies and neurophysiologic abnormalities in patients exposed to molds in water-damaged buildings.

    PubMed

    Campbell, Andrew W; Thrasher, Jack D; Madison, Roberta A; Vojdani, Aristo; Gray, Michael R; Johnson, Al

    2003-08-01

    Adverse health effects of fungal bioaerosols on occupants of water-damaged homes and other buildings have been reported. Recently, it has been suggested that mold exposure causes neurological injury. The authors investigated neurological antibodies and neurophysiological abnormalities in patients exposed to molds at home who developed symptoms of peripheral neuropathy (i.e., numbness, tingling, tremors, and muscle weakness in the extremities). Serum samples were collected and analyzed with the enzyme-linked immunosorbent assay (ELISA) technique for antibodies to myelin basic protein, myelin-associated glycoprotein, ganglioside GM1, sulfatide, myelin oligodendrocyte glycoprotein, alpha-B-crystallin, chondroitin sulfate, tubulin, and neurofilament. Antibodies to molds and mycotoxins were also determined with ELISA, as reported previously. Neurophysiologic evaluations for latency, amplitude, and velocity were performed on 4 motor nerves (median, ulnar, peroneal, and tibial), and for latency and amplitude on 3 sensory nerves (median, ulnar, and sural). Patients with documented, measured exposure to molds had elevated titers of antibodies (immunoglobulin [Ig]A, IgM, and IgG) to neural-specific antigens. Nerve conduction studies revealed 4 patient groupings: (1) mixed sensory-motor polyneuropathy (n = 55, abnormal), (2) motor neuropathy (n = 17, abnormal), (3) sensory neuropathy (n = 27, abnormal), and (4) those with symptoms but no neurophysiological abnormalities (n = 20, normal controls). All groups showed significantly increased autoantibody titers for all isotypes (IgA, IgM, and IgG) of antibodies to neural antigens when compared with 500 healthy controls. Groups 1 through 3 also exhibited abnormal neurophysiologic findings. The authors concluded that exposure to molds in water-damaged buildings increased the risk for development of neural autoantibodies, peripheral neuropathy, and neurophysiologic abnormalities in exposed individuals.

  16. Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

    PubMed

    VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

    2016-01-01

    People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

  17. Multidimensional analysis of the abnormal neural oscillations associated with lexical processing in schizophrenia.

    PubMed

    Xu, Tingting; Stephane, Massoud; Parhi, Keshab K

    2013-04-01

    The neural mechanisms of language abnormalities, the core symptoms in schizophrenia, remain unclear. In this study, a new experimental paradigm, combining magnetoencephalography (MEG) techniques and machine intelligence methodologies, was designed to gain knowledge about the frequency, brain location, and time of occurrence of the neural oscillations that are associated with lexical processing in schizophrenia. The 248-channel MEG recordings were obtained from 12 patients with schizophrenia and 10 healthy controls, during a lexical processing task, where the patients discriminated correct from incorrect lexical stimuli that were visually presented. Event-related desynchronization/synchronization (ERD/ERS) was computed along the frequency, time, and space dimensions combined, that resulted in a large spectral-spatial-temporal ERD/ERS feature set. Machine intelligence techniques were then applied to select a small subset of oscillation patterns that are abnormal in patients with schizophrenia, according to their discriminating power in patient and control classification. Patients with schizophrenia showed abnormal ERD/ERS patterns during both lexical encoding and post-encoding periods. The top-ranked features were located at the occipital and left frontal-temporal areas, and covered a wide frequency range, including δ (1-4 Hz), α (8-12 Hz), β (12-32 Hz), and γ (32-48 Hz) bands. These top features could discriminate the patient group from the control group with 90.91% high accuracy, which demonstrates significant brain oscillation abnormalities in patients with schizophrenia at the specific frequency, time, and brain location indicated by these top features. As neural oscillation abnormality may be due to the mechanisms of the disease, the spectral, spatial, and temporal content of the discriminating features can offer useful information for helping understand the physiological basis of the language disorder in schizophrenia, as well as the pathology of the

  18. Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa.

    PubMed

    Holsen, Laura M; Lawson, Elizabeth A; Christensen, Kara; Klibanski, Anne; Goldstein, Jill M

    2014-08-30

    Evidence contributing to the understanding of neurobiological mechanisms underlying appetite dysregulation in anorexia nervosa draws heavily on separate lines of research into neuroendocrine and neural circuitry functioning. In particular, studies consistently cite elevated ghrelin and abnormal activation patterns in homeostatic (hypothalamus) and hedonic (striatum, amygdala, insula) regions governing appetite. The current preliminary study examined the interaction of these systems, based on research demonstrating associations between circulating ghrelin levels and activity in these regions in healthy individuals. In a cross-sectional design, we studied 13 women with active anorexia nervosa (AN), 9 women weight-recovered from AN (AN-WR), and 12 healthy-weight control women using a food cue functional magnetic resonance imaging paradigm, with assessment of fasting levels of acylated ghrelin. Healthy-weight control women exhibited significant positive associations between fasting acylated ghrelin and activity in the right amygdala, hippocampus, insula, and orbitofrontal cortex in response to high-calorie foods, associations which were absent in the AN and AN-WR groups. Women with AN-WR demonstrated a negative relationship between ghrelin and activity in the left hippocampus in response to high-calorie foods, while women with AN showed a positive association between ghrelin and activity in the right orbitofrontal cortex in response to low-calorie foods. Findings suggest a breakdown in the interaction between ghrelin signaling and neural activity in relation to reward responsivity in AN, a phenomenon that may be further characterized using pharmacogenetic studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa

    PubMed Central

    Holsen, Laura M.; Lawson, Elizabeth A.; Christensen, Kara; Klibanski, Anne; Goldstein, Jill M.

    2014-01-01

    Evidence contributing to the understanding of neurobiological mechanisms underlying appetite dysregulation in anorexia nervosa draws heavily on separate lines of research into neuroendocrine and neural circuitry functioning. In particular, studies consistently cite elevated ghrelin and abnormal activation patterns in homeostatic (hypothalamus) and hedonic (striatum, amygdala, insula) regions governing appetite. The current preliminary study examined the interaction of these systems, based on research demonstrating associations between circulating ghrelin levels and activity in these regions in healthy individuals. In a cross-sectional design, we studied 13 women with active anorexia nervosa (AN), 9 women weight-recovered from AN (AN-WR), and 12 healthy-weight control women using a food cue functional magnetic resonance imaging paradigm, with assessment of fasting levels of acylated ghrelin. Healthy-weight control women exhibited significant positive associations between fasting acylated ghrelin and activity in the right amygdala, hippocampus, insula, and orbitofrontal cortex in response to high-calorie foods, associations which were absent in the AN and AN-WR groups. Women with AN-WR demonstrated a negative relationship between ghrelin and activity in the left hippocampus in response to high-calorie foods, while women with AN showed a positive association between ghrelin and activity in the right orbitofrontal cortex in response to low-calorie foods. Findings suggest a breakdown in the interaction between ghrelin signaling and neural activity in relation to reward responsivity in AN, a phenomenon that may be further characterized using pharmacogenetic studies. PMID:24862390

  20. Neural responses to gains and losses in children of suicide attempters.

    PubMed

    Tsypes, Aliona; Owens, Max; Hajcak, Greg; Gibb, Brandon E

    2017-02-01

    [Correction Notice: An Erratum for this article was reported in Vol 126(2) of Journal of Abnormal Psychology (see record 2016-56318-001). In the article, Figure 1 had incorrect axis labels. There was also an error in the abstract, which did not state that ΔFN was calculated as FN to losses minus FN to gains. All versions of this article have been corrected.] Suicidal behavior aggregates within families, yet the specific mechanisms of suicide-risk transmission are poorly understood. Despite some evidence that abnormal patterns of reward responsiveness might constitute one such potential mechanism, empirical evidence is lacking. The goal of this study was to examine neural responses to gains and losses in children of suicide attempters with no personal history of suicide attempt (SA) themselves. To objectively assess these neural responses, we used feedback negativity (FN), a psychophysiological marker of responsiveness to reward and loss. Participants were 66 parents and their 7-11-year-old children (22 with parental history of SA and 44 demographically and clinically matched children of parents with no SA history). Diagnostic interviews were used to gather information about psychiatric diagnoses, symptoms, and histories of suicidal thoughts and behaviors. Children also completed a guessing task, during which continuous electroencephalography (EEG) was recorded. The FN was scored as the mean amplitude, 275-375 ms, following gain or loss feedback at frontocentral sites (Fz and FCz). Children of suicide attempters exhibited significantly more negative ΔFN (i.e., FN to losses minus FN to gains) than children of parents with no SA history. We found that this difference in ΔFN was due specifically to children of parents with a history of SA exhibiting a stronger response to loss, and no group differences were observed for responses to gains. The results suggest that an increased neural response to loss might represent one of the potential pathways of the familial

  1. Neural correlates of genetically abnormal social cognition in Williams syndrome.

    PubMed

    Meyer-Lindenberg, Andreas; Hariri, Ahmad R; Munoz, Karen E; Mervis, Carolyn B; Mattay, Venkata S; Morris, Colleen A; Berman, Karen Faith

    2005-08-01

    Williams-Beuren syndrome (WBS), caused by a microdeletion of approximately 21 genes on chromosome 7q11.23, is characterized by unique hypersociability combined with increased non-social anxiety. Using functional neuroimaging, we found reduced amygdala activation in individuals with WBS for threatening faces but increased activation for threatening scenes, relative to matched normal controls. Activation and interactions of prefrontal regions linked to amygdala, especially orbitofrontal cortex, were abnormal, suggesting a genetically controlled neural circuitry for regulating human social behavior.

  2. Cell death in neural precursor cells and neurons before neurite formation prevents the emergence of abnormal neural structures in the Drosophila optic lobe.

    PubMed

    Hara, Yusuke; Sudo, Tatsuya; Togane, Yu; Akagawa, Hiromi; Tsujimura, Hidenobu

    2018-04-01

    Programmed cell death is a conserved strategy for neural development both in vertebrates and invertebrates and is recognized at various developmental stages in the brain from neurogenesis to adulthood. To understand the development of the central nervous system, it is essential to reveal not only molecular mechanisms but also the role of neural cell death (Pinto-Teixeira et al., 2016). To understand the role of cell death in neural development, we investigated the effect of inhibition of cell death on optic lobe development. Our data demonstrate that, in the optic lobe of Drosophila, cell death occurs in neural precursor cells and neurons before neurite formation and functions to prevent various developmental abnormalities. When neuronal cell death was inhibited by an effector caspase inhibitor, p35, multiple abnormal neuropil structures arose during optic lobe development-e.g., enlarged or fused neuropils, misrouted neurons and abnormal neurite lumps. Inhibition of cell death also induced morphogenetic defects in the lamina and medulla development-e.g., failures in the separation of the lamina and medulla cortices and the medulla rotation. These defects were reproduced in the mutant of an initiator caspase, dronc. If cell death was a mechanism for removing the abnormal neuropil structures, we would also expect to observe them in mutants defective for corpse clearance. However, they were not observed in these mutants. When dead cell-membranes were visualized with Apoliner, they were observed only in cortices and not in neuropils. These results suggest that the cell death occurs before mature neurite formation. Moreover, we found that inhibition of cell death induced ectopic neuroepithelial cells, neuroblasts and ganglion mother cells in late pupal stages, at sites where the outer and inner proliferation centers were located at earlier developmental stages. Caspase-3 activation was observed in the neuroepithelial cells and neuroblasts in the proliferation centers

  3. Abnormal Neural Connectivity in Schizophrenia and fMRI-Brain-Computer Interface as a Potential Therapeutic Approach

    PubMed Central

    Ruiz, Sergio; Birbaumer, Niels; Sitaram, Ranganatha

    2012-01-01

    Considering that single locations of structural and functional abnormalities are insufficient to explain the diverse psychopathology of schizophrenia, new models have postulated that the impairments associated with the disease arise from a failure to integrate the activity of local and distributed neural circuits: the “abnormal neural connectivity hypothesis.” In the last years, new evidence coming from neuroimaging have supported and expanded this theory. However, despite the increasing evidence that schizophrenia is a disorder of neural connectivity, so far there are no treatments that have shown to produce a significant change in brain connectivity, or that have been specifically designed to alleviate this problem. Brain-Computer Interfaces based on real-time functional Magnetic Resonance Imaging (fMRI-BCI) are novel techniques that have allowed subjects to achieve self-regulation of circumscribed brain regions. In recent studies, experiments with this technology have resulted in new findings suggesting that this methodology could be used to train subjects to enhance brain connectivity, and therefore could potentially be used as a therapeutic tool in mental disorders including schizophrenia. The present article summarizes the findings coming from hemodynamics-based neuroimaging that support the abnormal connectivity hypothesis in schizophrenia, and discusses a new approach that could address this problem. PMID:23525496

  4. Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities

    PubMed Central

    Dixon, Jill; Jones, Natalie C.; Sandell, Lisa L.; Jayasinghe, Sachintha M.; Crane, Jennifer; Rey, Jean-Philippe; Dixon, Michael J.; Trainor, Paul A.

    2006-01-01

    Neural crest cells are a migratory cell population that give rise to the majority of the cartilage, bone, connective tissue, and sensory ganglia in the head. Abnormalities in the formation, proliferation, migration, and differentiation phases of the neural crest cell life cycle can lead to craniofacial malformations, which constitute one-third of all congenital birth defects. Treacher Collins syndrome (TCS) is characterized by hypoplasia of the facial bones, cleft palate, and middle and external ear defects. Although TCS results from autosomal dominant mutations of the gene TCOF1, the mechanistic origins of the abnormalities observed in this condition are unknown, and the function of Treacle, the protein encoded by TCOF1, remains poorly understood. To investigate the developmental basis of TCS we generated a mouse model through germ-line mutation of Tcof1. Haploinsufficiency of Tcof1 leads to a deficiency in migrating neural crest cells, which results in severe craniofacial malformations. We demonstrate that Tcof1/Treacle is required cell-autonomously for the formation and proliferation of neural crest cells. Tcof1/Treacle regulates proliferation by controlling the production of mature ribosomes. Therefore, Tcof1/Treacle is a unique spatiotemporal regulator of ribosome biogenesis, a deficiency that disrupts neural crest cell formation and proliferation, causing the hypoplasia characteristic of TCS craniofacial anomalies. PMID:16938878

  5. Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities.

    PubMed

    Dixon, Jill; Jones, Natalie C; Sandell, Lisa L; Jayasinghe, Sachintha M; Crane, Jennifer; Rey, Jean-Philippe; Dixon, Michael J; Trainor, Paul A

    2006-09-05

    Neural crest cells are a migratory cell population that give rise to the majority of the cartilage, bone, connective tissue, and sensory ganglia in the head. Abnormalities in the formation, proliferation, migration, and differentiation phases of the neural crest cell life cycle can lead to craniofacial malformations, which constitute one-third of all congenital birth defects. Treacher Collins syndrome (TCS) is characterized by hypoplasia of the facial bones, cleft palate, and middle and external ear defects. Although TCS results from autosomal dominant mutations of the gene TCOF1, the mechanistic origins of the abnormalities observed in this condition are unknown, and the function of Treacle, the protein encoded by TCOF1, remains poorly understood. To investigate the developmental basis of TCS we generated a mouse model through germ-line mutation of Tcof1. Haploinsufficiency of Tcof1 leads to a deficiency in migrating neural crest cells, which results in severe craniofacial malformations. We demonstrate that Tcof1/Treacle is required cell-autonomously for the formation and proliferation of neural crest cells. Tcof1/Treacle regulates proliferation by controlling the production of mature ribosomes. Therefore, Tcof1/Treacle is a unique spatiotemporal regulator of ribosome biogenesis, a deficiency that disrupts neural crest cell formation and proliferation, causing the hypoplasia characteristic of TCS craniofacial anomalies.

  6. Abnormal Neural Activation to Faces in the Parents of Children with Autism

    PubMed Central

    Yucel, G. H.; Belger, A.; Bizzell, J.; Parlier, M.; Adolphs, R.; Piven, J.

    2015-01-01

    Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the “Broad Autism Phenotype ” (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality (“BAP+”). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. PMID:25056573

  7. Increased neural responses to reward in adolescents and young adults with attention-deficit/hyperactivity disorder and their unaffected siblings.

    PubMed

    von Rhein, Daniel; Cools, Roshan; Zwiers, Marcel P; van der Schaaf, Marieke; Franke, Barbara; Luman, Marjolein; Oosterlaan, Jaap; Heslenfeld, Dirk J; Hoekstra, Pieter J; Hartman, Catharina A; Faraone, Stephen V; van Rooij, Daan; van Dongen, Eelco V; Lojowska, Maria; Mennes, Maarten; Buitelaar, Jan

    2015-05-01

    Attention-deficit/hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder associated with abnormal reward processing. Limited and inconsistent data exist about the neural mechanisms underlying this abnormality. Furthermore, it is not known whether reward processing is abnormal in unaffected siblings of participants with ADHD. We used event-related functional magnetic resonance imaging (fMRI) to investigate brain responses during reward anticipation and receipt with an adapted monetary incentive delay task in a large sample of adolescents and young adults with ADHD (n = 150), their unaffected siblings (n = 92), and control participants (n = 108), all of the same age. Participants with ADHD showed, relative to control participants, increased responses in the anterior cingulate, anterior frontal cortex, and cerebellum during reward anticipation, and in the orbitofrontal, occipital cortex and ventral striatum. Responses of unaffected siblings were increased in these regions as well, except for the cerebellum during anticipation and ventral striatum during receipt. ADHD in adolescents and young adults is associated with enhanced neural responses in frontostriatal circuitry to anticipation and receipt of reward. The findings support models emphasizing aberrant reward processing in ADHD, and suggest that processing of reward is subject to familial influences. Future studies using standard monetary incentive delay task parameters are needed to replicate our findings. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  8. Abnormal Neural Activation to Faces in the Parents of Children with Autism.

    PubMed

    Yucel, G H; Belger, A; Bizzell, J; Parlier, M; Adolphs, R; Piven, J

    2015-12-01

    Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the "Broad Autism Phenotype " (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality ("BAP+"). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Exploring non-stationarity patterns in schizophrenia: neural reorganization abnormalities in the alpha band

    NASA Astrophysics Data System (ADS)

    Núñez, Pablo; Poza, Jesús; Bachiller, Alejandro; Gomez-Pilar, Javier; Lubeiro, Alba; Molina, Vicente; Hornero, Roberto

    2017-08-01

    Objective. The aim of this paper was to characterize brain non-stationarity during an auditory oddball task in schizophrenia (SCH). The level of non-stationarity was measured in the baseline and response windows of relevant tones in SCH patients and healthy controls. Approach. Event-related potentials were recorded from 28 SCH patients and 51 controls. Non-stationarity was estimated in the conventional electroencephalography frequency bands by means of Kullback-Leibler divergence (KLD). Relative power (RP) was also computed to assess a possible complementarity with KLD. Main results. Results showed a widespread statistically significant increase in the level of non-stationarity from baseline to response in all frequency bands for both groups. Statistically significant differences in non-stationarity were found between SCH patients and controls in beta-2 and in the alpha band. SCH patients showed more non-stationarity in the left parieto-occipital region during the baseline window in the beta-2 band. A leave-one-out cross validation classification study with feature selection based on binary stepwise logistic regression to discriminate between SCH patients and controls provided a positive predictive value of 72.73% and negative predictive value of 78.95%. Significance. KLD can characterize transient neural reorganization during an attentional task in response to novelty and relevance. Our findings suggest anomalous reorganization of neural dynamics in SCH during an oddball task. The abnormal frequency-dependent modulation found in SCH patients during relevant tones is in agreement with the hypothesis of aberrant salience detection in SCH. The increase in non-stationarity in the alpha band during the active task supports the notion that this band is involved in top-down processing. The baseline differences in the beta-2 band suggest that hyperactivation of the default mode network during attention tasks may be related to SCH symptoms. Furthermore, the classification

  10. Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

    PubMed

    Sourial, Mary; Doering, Laurie C

    2017-07-01

    The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  11. Neural response to working memory demand predicts neurocognitive deficits in HIV.

    PubMed

    Cohen, Ronald A; Siegel, S; Gullett, J M; Porges, E; Woods, A J; Huang, H; Zhu, Y; Tashima, K; Ding, M-Z

    2018-06-01

    Human immunodeficiency virus (HIV) continues to have adverse effects on cognition and the brain in many infected people, despite a reduced incidence of HIV-associated dementia with combined antiretroviral therapy (cART). Working memory is often affected, along with attention, executive control, and cognitive processing speed. Verbal working memory (VWM) requires the interaction of each of the cognitive component processes along with a phonological loop for verbal repetition and rehearsal. HIV-related functional brain response abnormalities during VWM are evident in functional MRI (fMRI), though the neural substrate underlying these neurocognitive deficits is not well understood. The current study addressed this by comparing 24 HIV+ to 27 demographically matched HIV-seronegative (HIV-) adults with respect to fMRI activation on a VWM paradigm (n-back) relative to performance on two standardized tests of executive control, attention and processing speed (Stroop and Trail Making A-B). As expected, the HIV+ group had deficits on these neurocognitive tests compared to HIV- controls, and also differed in neural response on fMRI relative to neuropsychological performance. Reduced activation in VWM task-related brain regions on the 2-back was associated with Stroop interference deficits in HIV+ but not with either Trail Making A or B performance. Activation of the posterior cingulate cortex (PCC) of the default mode network during rest was associated with Hopkins Verbal Learning Test-2 (HVLT-2) learning in HIV+. These effects were not observed in the HIV- controls. Reduced dynamic range of neural response was also evident in HIV+ adults when activation on the 2-back condition was compared to the extent of activation of the default mode network during periods of rest. Neural dynamic range was associated with both Stroop and HVLT-2 performance. These findings provide evidence that HIV-associated alterations in neural activation induced by VWM demands and during rest

  12. Neural correlates of emotional response inhibition in obsessive-compulsive disorder: A preliminary study.

    PubMed

    Berlin, Heather A; Schulz, Kurt P; Zhang, Sam; Turetzky, Rachel; Rosenthal, David; Goodman, Wayne

    2015-11-30

    Failure to inhibit recurrent anxiety-provoking thoughts is a central symptom of obsessive-compulsive disorder (OCD). Neuroimaging studies suggest inhibitory control and disgust processing abnormalities in patients with OCD. However, the emotional modulation of response inhibition deficits in OCD and their neural correlates remain to be elucidated. For this preliminary study we administered an adapted affective response inhibition paradigm, an emotional go/no-go task, during fMRI to characterize the neural systems underlying disgust-related and fear-related inhibition in nine adults with contamination-type OCD compared to ten matched healthy controls. Participants with OCD had significantly greater anterior insula cortex activation when inhibiting responses to both disgusting (bilateral), and fearful (right-sided) images, compared to healthy controls. They also had increased activation in several frontal, temporal, and parietal regions, but there was no evidence of amygdala activation in OCD or healthy participants and no significant between-group differences in performance on the emotion go/no-go task. The anterior insula appears to play a central role in the emotional modulation of response inhibition in contamination-type OCD to both fearful and disgusting images. The insula may serve as a potential treatment target for contamination-type OCD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Abnormal Neural Network of Primary Insomnia: Evidence from Spatial Working Memory Task fMRI.

    PubMed

    Li, Yongli; Liu, Liya; Wang, Enfeng; Zhang, Hongju; Dou, Shewei; Tong, Li; Cheng, Jingliang; Chen, Chuanliang; Shi, Dapeng

    2016-01-01

    Contemporary functional MRI (fMRI) methods can provide a wealth of information about the neural mechanisms associated with primary insomnia (PI), which centrally involve neural network circuits related to spatial working memory. A total of 30 participants diagnosed with PI and without atypical brain anatomy were selected along with 30 age- and gender-matched healthy controls. Subjects were administered the Pittsburgh Sleep Quality Index (PSQI), Hamilton Rating Scale for Depression and clinical assessments of spatial working memory, followed by an MRI scan and fMRI in spatial memory task state. Statistically significant differences between PSQI and spatial working memory were observed between PI patients and controls (p < 0.01). Activation of neural networks related to spatial memory task state in the PI group was observed at the left temporal lobe, left occipital lobe and right frontal lobe. Lower levels of activation were observed in the left parahippocampal gyrus, right parahippocampal gyrus, bilateral temporal cortex, frontal cortex and superior parietal lobule. Participants with PI exhibited characteristic abnormalities in the neural network connectivity related to spatial working memory. These results may be indicative of an underlying pathological mechanism related to spatial working memory deterioration in PI, analogous to recently described mechanisms in other mental health disorders. © 2016 S. Karger AG, Basel.

  14. Attention Alters Neural Responses to Evocative Faces in Behaviorally Inhibited Adolescents

    PubMed Central

    Pérez-Edgar, Koraly; Roberson-Nay, Roxann; Hardin, Michael G.; Poeth, Kaitlin; Guyer, Amanda E.; Nelson, Eric E.; McClure, Erin B.; Henderson, Heather A.; Fox, Nathan A.; Pine, Daniel S.; Ernst, Monique

    2007-01-01

    Behavioral inhibition (BI) is a risk factor for anxiety disorders. While the two constructs bear behavioral similarities, previous work has not extended these parallels to the neural level. This study examined amygdala reactivity during a task previously used with clinically anxious adolescents. Adolescents were selected for enduring patterns of BI or non-inhibition (BN). We examined amygdala response to evocative emotion faces in BI (N=10, mean 12.8 years) and BN (N=17, mean 12.5 years) adolescents while systematically manipulating attention. Analyses focused on amygdala response during subjective ratings of internal fear (constrained attention) and passive viewing (unconstrained attention) during the presentation of emotion faces (Happy, Angry, Fearful, and Neutral). BI adolescents, relative to BN adolescents, showed exaggerated amygdala response during subjective fear ratings and deactivation during passive viewing, across all emotion faces. In addition, the BI group showed an abnormally high amygdala response to a task condition marked by novelty and uncertainty (i.e., rating fear state to a Happy face). Perturbations in amygdala function are evident in adolescents temperamentally at risk for anxiety. Attention state alters the underlying pattern of neural processing, potentially mediating the observed behavioral patterns across development. BI adolescents also show a heightened sensitivity to novelty and uncertainty, which has been linked to anxiety. These patterns of reactivity may help sustain early temperamental biases over time and contribute to the observed relation between BI and anxiety. PMID:17376704

  15. Can responses to basic non-numerical visual features explain neural numerosity responses?

    PubMed

    Harvey, Ben M; Dumoulin, Serge O

    2017-04-01

    Humans and many animals can distinguish between stimuli that differ in numerosity, the number of objects in a set. Human and macaque parietal lobes contain neurons that respond to changes in stimulus numerosity. However, basic non-numerical visual features can affect neural responses to and perception of numerosity, and visual features often co-vary with numerosity. Therefore, it is debated whether numerosity or co-varying low-level visual features underlie neural and behavioral responses to numerosity. To test the hypothesis that non-numerical visual features underlie neural numerosity responses in a human parietal numerosity map, we analyze responses to a group of numerosity stimulus configurations that have the same numerosity progression but vary considerably in their non-numerical visual features. Using ultra-high-field (7T) fMRI, we measure responses to these stimulus configurations in an area of posterior parietal cortex whose responses are believed to reflect numerosity-selective activity. We describe an fMRI analysis method to distinguish between alternative models of neural response functions, following a population receptive field (pRF) modeling approach. For each stimulus configuration, we first quantify the relationships between numerosity and several non-numerical visual features that have been proposed to underlie performance in numerosity discrimination tasks. We then determine how well responses to these non-numerical visual features predict the observed fMRI responses, and compare this to the predictions of responses to numerosity. We demonstrate that a numerosity response model predicts observed responses more accurately than models of responses to simple non-numerical visual features. As such, neural responses in cognitive processing need not reflect simpler properties of early sensory inputs. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Abnormal fronto-limbic engagement in incarcerated stimulant users during moral processing.

    PubMed

    Fede, Samantha J; Harenski, Carla L; Schaich Borg, Jana; Sinnott-Armstrong, Walter; Rao, Vikram; Caldwell, Brendan M; Nyalakanti, Prashanth K; Koenigs, Michael R; Decety, Jean; Calhoun, Vince D; Kiehl, Kent A

    2016-09-01

    Stimulant use is a significant and prevalent problem, particularly in criminal populations. Previous studies found that cocaine and methamphetamine use is related to impairment in identifying emotions and empathy. Stimulant users also have abnormal neural structure and function of the ventromedial prefrontal cortex (vmPFC), amygdala, and anterior (ACC) and posterior cingulate (PCC), regions implicated in moral decision-making. However, no research has studied the neural correlates of stimulant use and explicit moral processing in an incarcerated population. Here, we examine how stimulant use affects sociomoral processing that might contribute to antisocial behavior. We predicted that vmPFC, amygdala, PCC, and ACC would show abnormal neural response during a moral processing task in incarcerated methamphetamine and cocaine users. Incarcerated adult males (N = 211) were scanned with a mobile MRI system while completing a moral decision-making task. Lifetime drug use was assessed. Neural responses during moral processing were compared between users and non-users. The relationship between duration of use and neural function was also examined. Incarcerated stimulant users showed less amygdala engagement than non-users during moral processing. Duration of stimulant use was negatively associated with activity in ACC and positively associated with vmPFC response during moral processing. These results suggest a dynamic pattern of fronto-limbic moral processing related to stimulant use with deficits in both central motive and cognitive integration elements of biological moral processes theory. This increases our understanding of how drug use relates to moral processing in the brain in an ultra-high-risk population.

  17. Infrared neural stimulation (INS) inhibits electrically evoked neural responses in the deaf white cat

    NASA Astrophysics Data System (ADS)

    Richter, Claus-Peter; Rajguru, Suhrud M.; Robinson, Alan; Young, Hunter K.

    2014-03-01

    Infrared neural stimulation (INS) has been used in the past to evoke neural activity from hearing and partially deaf animals. All the responses were excitatory. In Aplysia californica, Duke and coworkers demonstrated that INS also inhibits neural responses [1], which similar observations were made in the vestibular system [2, 3]. In deaf white cats that have cochleae with largely reduced spiral ganglion neuron counts and a significant degeneration of the organ of Corti, no cochlear compound action potentials could be observed during INS alone. However, the combined electrical and optical stimulation demonstrated inhibitory responses during irradiation with infrared light.

  18. Racial bias in neural empathic responses to pain.

    PubMed

    Contreras-Huerta, Luis Sebastian; Baker, Katharine S; Reynolds, Katherine J; Batalha, Luisa; Cunnington, Ross

    2013-01-01

    Recent studies have shown that perceiving the pain of others activates brain regions in the observer associated with both somatosensory and affective-motivational aspects of pain, principally involving regions of the anterior cingulate and anterior insula cortex. The degree of these empathic neural responses is modulated by racial bias, such that stronger neural activation is elicited by observing pain in people of the same racial group compared with people of another racial group. The aim of the present study was to examine whether a more general social group category, other than race, could similarly modulate neural empathic responses and perhaps account for the apparent racial bias reported in previous studies. Using a minimal group paradigm, we assigned participants to one of two mixed-race teams. We use the term race to refer to the Chinese or Caucasian appearance of faces and whether the ethnic group represented was the same or different from the appearance of the participant' own face. Using fMRI, we measured neural empathic responses as participants observed members of their own group or other group, and members of their own race or other race, receiving either painful or non-painful touch. Participants showed clear group biases, with no significant effect of race, on behavioral measures of implicit (affective priming) and explicit group identification. Neural responses to observed pain in the anterior cingulate cortex, insula cortex, and somatosensory areas showed significantly greater activation when observing pain in own-race compared with other-race individuals, with no significant effect of minimal groups. These results suggest that racial bias in neural empathic responses is not influenced by minimal forms of group categorization, despite the clear association participants showed with in-group more than out-group members. We suggest that race may be an automatic and unconscious mechanism that drives the initial neural responses to observed pain in

  19. Racial Bias in Neural Empathic Responses to Pain

    PubMed Central

    Contreras-Huerta, Luis Sebastian; Baker, Katharine S.; Reynolds, Katherine J.; Batalha, Luisa; Cunnington, Ross

    2013-01-01

    Recent studies have shown that perceiving the pain of others activates brain regions in the observer associated with both somatosensory and affective-motivational aspects of pain, principally involving regions of the anterior cingulate and anterior insula cortex. The degree of these empathic neural responses is modulated by racial bias, such that stronger neural activation is elicited by observing pain in people of the same racial group compared with people of another racial group. The aim of the present study was to examine whether a more general social group category, other than race, could similarly modulate neural empathic responses and perhaps account for the apparent racial bias reported in previous studies. Using a minimal group paradigm, we assigned participants to one of two mixed-race teams. We use the term race to refer to the Chinese or Caucasian appearance of faces and whether the ethnic group represented was the same or different from the appearance of the participant' own face. Using fMRI, we measured neural empathic responses as participants observed members of their own group or other group, and members of their own race or other race, receiving either painful or non-painful touch. Participants showed clear group biases, with no significant effect of race, on behavioral measures of implicit (affective priming) and explicit group identification. Neural responses to observed pain in the anterior cingulate cortex, insula cortex, and somatosensory areas showed significantly greater activation when observing pain in own-race compared with other-race individuals, with no significant effect of minimal groups. These results suggest that racial bias in neural empathic responses is not influenced by minimal forms of group categorization, despite the clear association participants showed with in-group more than out-group members. We suggest that race may be an automatic and unconscious mechanism that drives the initial neural responses to observed pain in

  20. Neural processing of reward and punishment in young people at increased familial risk of depression.

    PubMed

    McCabe, Ciara; Woffindale, Caroline; Harmer, Catherine J; Cowen, Philip J

    2012-10-01

    Abnormalities in the neural representation of rewarding and aversive stimuli have been well-described in patients with acute depression, and we previously found abnormal neural responses to rewarding and aversive sight and taste stimuli in recovered depressed patients. The aim of the present study was to determine whether similar abnormalities might be present in young people at increased familial risk of depression but with no personal history of mood disorder. We therefore used functional magnetic resonance imaging to examine the neural responses to pleasant and aversive sights and tastes in 25 young people (16-21 years of age) with a biological parent with depression and 25 age- and gender-matched control subjects. We found that, relative to the control subjects, participants with a parental history of depression showed diminished responses in the orbitofrontal cortex to rewarding stimuli, whereas activations to aversive stimuli were increased in the lateral orbitofrontal cortex and insula. In anterior cingulate cortex the at-risk group showed blunted neural responses to both rewarding and aversive stimuli. Our findings suggest that young people at increased familial risk of depression have altered neural representation of reward and punishment, particularly in cortical regions linked to the use of positive and negative feedback to guide adaptive behavior. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

    PubMed

    Xu, Long-Chun; Zhang, Gang; Zou, Yue; Zhang, Min-Feng; Zhang, Dong-Sheng; Ma, Hua; Zhao, Wen-Bo; Zhang, Guang-Yu

    2017-10-13

    The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

  2. Neural responses to feedback information produced by self-generated or other-generated decision-making and their impairment in schizophrenia.

    PubMed

    Toyomaki, Atsuhito; Hashimoto, Naoki; Kako, Yuki; Murohashi, Harumitsu; Kusumi, Ichiro

    2017-01-01

    Several studies of self-monitoring dysfunction in schizophrenia have focused on the sense of agency to motor action using behavioral and psychophysiological techniques. So far, no study has ever tried to investigate whether the sense of agency or causal attribution for external events produced by self-generated decision-making is abnormal in schizophrenia. The purpose of this study was to investigate neural responses to feedback information produced by self-generated or other-generated decision-making in a multiplayer gambling task using even-related potentials and electroencephalogram synchronization. We found that the late positive component and theta/alpha synchronization were increased in response to feedback information in the self-decision condition in normal controls, but that these responses were significantly decreased in patients with schizophrenia. These neural activities thus reflect the self-reference effect that affects the cognitive appraisal of external events following decision-making and their impairment in schizophrenia.

  3. Family history of psychosis moderates early auditory cortical response abnormalities in non-psychotic bipolar disorder

    PubMed Central

    Hamm, Jordan P; Ethridge, Lauren E; Shapiro, John R; Pearlson, Godfrey D; Tamminga, Carol A; Sweeney, John A; Keshavan, Matcheri S; Thaker, Gunvant K; Clementz, Brett A

    2017-01-01

    Objectives Bipolar I disorder is a disabling illness affecting 1% of people worldwide. Family and twin studies suggest that psychotic bipolar disorder (BDP) represents a homogenous subgroup with an etiology distinct from non-psychotic bipolar disorder (BDNP) and partially shared with schizophrenia. Studies of auditory electrophysiology [e.g., paired-stimulus and oddball measured with electroencephalography (EEG)] consistently report deviations in psychotic groups (schizophrenia, BDP), yet such studies comparing BDP and BDNP are sparse and, in some cases, conflicting. Auditory EEG responses are significantly reduced in unaffected relatives of psychosis patients, suggesting that they may relate to both psychosis liability and expression. Methods While 64-sensor EEGs were recorded, age- and gender-matched samples of 70 BDP, 35 BDNP {20 with a family history of psychosis [BDNP(+)]}, and 70 psychiatrically healthy subjects were presented typical auditory paired-stimuli and auditory oddball paradigms. Results Oddball P3b reductions were present and indistinguishable across all patient groups. P2s to paired-stimuli were abnormal only in BDP and BDNP(+). Conversely, N1 reductions to stimuli in both paradigms and P3a reductions were present in both BDP and BDNP(−) groups but were absent in BDNP(+). Conclusions While nearly all auditory neural response components studied were abnormal in BDP, BDNP abnormalities at early- and mid-latencies were moderated by family psychosis history. The relationship between psychosis expression, heritable psychosis risk, and neurophysiology within bipolar disorder, therefore, may be complex. Consideration of such clinical disease heterogeneity may be important for future investigations of the pathophysiology of major psychiatric disturbance. PMID:23941660

  4. Unreliable evoked responses in autism

    PubMed Central

    Dinstein, Ilan; Heeger, David J.; Lorenzi, Lauren; Minshew, Nancy J.; Malach, Rafael; Behrmann, Marlene

    2012-01-01

    Summary Autism has been described as a disorder of general neural processing, but the particular processing characteristics that might be abnormal in autism have mostly remained obscure. Here, we present evidence of one such characteristic: poor evoked response reliability. We compared cortical response amplitude and reliability (consistency across trials) in visual, auditory, and somatosensory cortices of high-functioning individuals with autism and controls. Mean response amplitudes were statistically indistinguishable across groups, yet trial-by-trial response reliability was significantly weaker in autism, yielding smaller signal-to-noise ratios in all sensory systems. Response reliability differences were evident only in evoked cortical responses and not in ongoing resting-state activity. These findings reveal that abnormally unreliable cortical responses, even to elementary non-social sensory stimuli, may represent a fundamental physiological alteration of neural processing in autism. The results motivate a critical expansion of autism research to determine whether (and how) basic neural processing properties such as reliability, plasticity, and adaptation/habituation are altered in autism. PMID:22998867

  5. Antipsychotic dose modulates behavioral and neural responses to feedback during reinforcement learning in schizophrenia.

    PubMed

    Insel, Catherine; Reinen, Jenna; Weber, Jochen; Wager, Tor D; Jarskog, L Fredrik; Shohamy, Daphna; Smith, Edward E

    2014-03-01

    Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.

  6. Prevention of congenital abnormalities by periconceptional multivitamin supplementation.

    PubMed Central

    Czeizel, A E

    1993-01-01

    OBJECTIVE--To study the effect of periconceptional multivitamin supplementation on neural tube defects and other congenital abnormality entities. DESIGN--Randomised controlled trial of supplementation with multivitamins and trace elements. SETTING--Hungarian family planning programme. SUBJECTS--4156 pregnancies with known outcome and 3713 infants evaluated in the eighth month of life. INTERVENTIONS--A single tablet of a multivitamin including 0.8 mg of folic acid or trace elements supplement daily for at least one month before conception and at least two months after conception. MAIN OUTCOME MEASURES--Number of major and mild congenital abnormalities. RESULTS--The rate of all major congenital abnormalities was significantly lower in the group given vitamins than in the group given trace elements and this difference cannot be explained totally by the significant reduction of neural tube defects. The rate of major congenital abnormalities other than neural tube defects and genetic syndromes was 9.0/1000 in pregnancies with known outcome in the vitamin group and 16.6/1000 in the trace element group; relative risk 1.85 (95% confidence interval 1.02 to 3.38); difference, 7.6/1000. The rate of all major congenital abnormalities other than neural tube defects and genetic syndromes diagnosed up to the eighth month of life was 14.7/1000 informative pregnancies in the vitamin group and 28.3/1000 in the trace element group; relative risk 1.95 (1.23 to 3.09); difference, 13.6/1000. The rate of some congenital abnormalities was lower in the vitamin group than in the trace element group but the differences for each group of abnormalities were not significant. CONCLUSIONS--Periconceptional multivitamin supplementation can reduce not only the rate of neural tube defects but also the rate of other major non-genetic syndromatic congenital abnormalities. Further studies are needed to differentiate the chance effect and vitamin dependent effect. PMID:8324432

  7. Progressive Changes in a Distributed Neural Circuit Underlie Breathing Abnormalities in Mice Lacking MeCP2.

    PubMed

    Huang, Teng-Wei; Kochukov, Mikhail Y; Ward, Christopher S; Merritt, Jonathan; Thomas, Kaitlin; Nguyen, Tiffani; Arenkiel, Benjamin R; Neul, Jeffrey L

    2016-05-18

    Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Severe breathing abnormalities are common in RTT and are reproduced in mouse models of RTT. Previously, we found that removing MeCP2 from the brainstem and spinal cord in mice caused early lethality and abnormal breathing. To determine whether loss of MeCP2 in functional components of the respiratory network causes specific breathing disorders, we used the Cre/LoxP system to differentially manipulate MeCP2 expression throughout the brainstem respiratory network, specifically within HoxA4-derived tissues, which include breathing control circuitry within the nucleus tractus solitarius and the caudal part of ventral respiratory column but do not include more rostral parts of the breathing control circuitry. To determine whether respiratory phenotypes manifested in animals with MeCP2 removed from specific pons medullary respiratory circuits, we performed whole-body plethysmography and electrophysiological recordings from in vitro brainstem slices from mice lacking MeCP2 in different circuits. Our results indicate that MeCP2 expression in the medullary respiratory network is sufficient for normal respiratory rhythm and preventing apnea. However, MeCP2 expression within components of the breathing circuitry rostral to the HoxA4 domain are neither sufficient to prevent the hyperventilation nor abnormal hypoxic ventilatory response. Surprisingly, we found that MeCP2 expression in the HoxA4 domain alone is critical for survival. Our study reveals that MeCP2 is differentially required in select respiratory components for different aspects of respiratory functions, and collectively for the integrity of this network functions to maintain proper respiration. Breathing abnormalities are a significant clinical feature in Rett syndrome and are robustly reproduced in the mouse models of this disease. Previous work has established that alterations in the function of Me

  8. Management of abnormal serum markers in the absence of aneuploidy or neural tube defects

    PubMed Central

    Schnettler, William T.; Hacker, Michele R.; Barber, Rachel E.; Rana, Sarosh

    2013-01-01

    Objective Few guidelines address the management of pregnancies complicated by abnormal maternal serum analytes (MSAs) in the absence of aneuploidy or neural tube defects (NTDs). Our objective was to gather preliminary data regarding current opinions and management strategies among perinatologists in the US. Methods This survey of Maternal Fetal Medicine (MFM) physicians and fellows used a secure electronic web-based data capture tool. Results A total of 545 potential participants were contacted, and 136 (25%) responded. The majority were experienced academic physicians with robust practices. Nearly all (97.7%) respondents reported a belief in an association between abnormal MSAs and adverse pregnancy outcomes other than aneuploidy or NTDs. Plasma protein A (PAPP-A) and α-fetoprotein (AFP) were most often chosen as markers demonstrating a strong association with adverse outcomes. Most (86.9%) respondents acknowledged that abnormal MSAs influenced their counseling approach, and the majority (80.1%) offered additional ultrasound examinations. Nearly half started at 28 weeks and almost one-third at 32 weeks. Respondents acknowledging a relevant protocol in their hospital or practice were more likely to offer additional antenatal testing (p = 0.01). Conclusions Although most perinatologists were in agreement regarding the association of MSAs with adverse pregnancy outcomes, a lack of consensus exists regarding management strategies. PMID:22372385

  9. Motivational orientation modulates the neural response to reward.

    PubMed

    Linke, Julia; Kirsch, Peter; King, Andrea V; Gass, Achim; Hennerici, Michael G; Bongers, André; Wessa, Michèle

    2010-02-01

    Motivational orientation defines the source of motivation for an individual to perform a particular action and can either originate from internal desires (e.g., interest) or external compensation (e.g., money). To this end, motivational orientation should influence the way positive or negative feedback is processed during learning situations and this might in turn have an impact on the learning process. In the present study, we thus investigated whether motivational orientation, i.e., extrinsic and intrinsic motivation modulates the neural response to reward and punishment as well as learning from reward and punishment in 33 healthy individuals. To assess neural responses to reward, punishment and learning of reward contingencies we employed a probabilistic reversal learning task during functional magnetic resonance imaging. Extrinsic and intrinsic motivation were assessed with a self-report questionnaire. Rewarding trials fostered activation in the medial orbitofrontal cortex and anterior cingulate gyrus (ACC) as well as the amygdala and nucleus accumbens, whereas for punishment an increased neural response was observed in the medial and inferior prefrontal cortex, the superior parietal cortex and the insula. High extrinsic motivation was positively correlated to increased neural responses to reward in the ACC, amygdala and putamen, whereas a negative relationship between intrinsic motivation and brain activation in these brain regions was observed. These findings show that motivational orientation indeed modulates the responsiveness to reward delivery in major components of the human reward system and therefore extends previous results showing a significant influence of individual differences in reward-related personality traits on the neural processing of reward. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  10. A Decline in Response Variability Improves Neural Signal Detection during Auditory Task Performance

    PubMed Central

    Buran, Bradley N.; Sen, Kamal; Semple, Malcolm N.; Sanes, Dan H.

    2016-01-01

    The detection of a sensory stimulus arises from a significant change in neural activity, but a sensory neuron's response is rarely identical to successive presentations of the same stimulus. Large trial-to-trial variability would limit the central nervous system's ability to reliably detect a stimulus, presumably affecting perceptual performance. However, if response variability were to decrease while firing rate remained constant, then neural sensitivity could improve. Here, we asked whether engagement in an auditory detection task can modulate response variability, thereby increasing neural sensitivity. We recorded telemetrically from the core auditory cortex of gerbils, both while they engaged in an amplitude-modulation detection task and while they sat quietly listening to the identical stimuli. Using a signal detection theory framework, we found that neural sensitivity was improved during task performance, and this improvement was closely associated with a decrease in response variability. Moreover, units with the greatest change in response variability had absolute neural thresholds most closely aligned with simultaneously measured perceptual thresholds. Our findings suggest that the limitations imposed by response variability diminish during task performance, thereby improving the sensitivity of neural encoding and potentially leading to better perceptual sensitivity. SIGNIFICANCE STATEMENT The detection of a sensory stimulus arises from a significant change in neural activity. However, trial-to-trial variability of the neural response may limit perceptual performance. If the neural response to a stimulus is quite variable, then the response on a given trial could be confused with the pattern of neural activity generated when the stimulus is absent. Therefore, a neural mechanism that served to reduce response variability would allow for better stimulus detection. By recording from the cortex of freely moving animals engaged in an auditory detection task, we

  11. Attention enhances contrast appearance via increased input baseline of neural responses

    PubMed Central

    Cutrone, Elizabeth K.; Heeger, David J.; Carrasco, Marisa

    2014-01-01

    Covert spatial attention increases the perceived contrast of stimuli at attended locations, presumably via enhancement of visual neural responses. However, the relation between perceived contrast and the underlying neural responses has not been characterized. In this study, we systematically varied stimulus contrast, using a two-alternative, forced-choice comparison task to probe the effect of attention on appearance across the contrast range. We modeled performance in the task as a function of underlying neural contrast-response functions. Fitting this model to the observed data revealed that an increased input baseline in the neural responses accounted for the enhancement of apparent contrast with spatial attention. PMID:25549920

  12. A Decline in Response Variability Improves Neural Signal Detection during Auditory Task Performance.

    PubMed

    von Trapp, Gardiner; Buran, Bradley N; Sen, Kamal; Semple, Malcolm N; Sanes, Dan H

    2016-10-26

    The detection of a sensory stimulus arises from a significant change in neural activity, but a sensory neuron's response is rarely identical to successive presentations of the same stimulus. Large trial-to-trial variability would limit the central nervous system's ability to reliably detect a stimulus, presumably affecting perceptual performance. However, if response variability were to decrease while firing rate remained constant, then neural sensitivity could improve. Here, we asked whether engagement in an auditory detection task can modulate response variability, thereby increasing neural sensitivity. We recorded telemetrically from the core auditory cortex of gerbils, both while they engaged in an amplitude-modulation detection task and while they sat quietly listening to the identical stimuli. Using a signal detection theory framework, we found that neural sensitivity was improved during task performance, and this improvement was closely associated with a decrease in response variability. Moreover, units with the greatest change in response variability had absolute neural thresholds most closely aligned with simultaneously measured perceptual thresholds. Our findings suggest that the limitations imposed by response variability diminish during task performance, thereby improving the sensitivity of neural encoding and potentially leading to better perceptual sensitivity. The detection of a sensory stimulus arises from a significant change in neural activity. However, trial-to-trial variability of the neural response may limit perceptual performance. If the neural response to a stimulus is quite variable, then the response on a given trial could be confused with the pattern of neural activity generated when the stimulus is absent. Therefore, a neural mechanism that served to reduce response variability would allow for better stimulus detection. By recording from the cortex of freely moving animals engaged in an auditory detection task, we found that variability

  13. Emotional Response Inhibition in Bipolar Disorder: A Functional Magnetic Resonance Imaging Study of Trait- and State-Related Abnormalities

    PubMed Central

    Hummer, Tom A.; Hulvershorn, Leslie A.; Karne, Harish S.; Gunn, Abigail D.; Wang, Yang; Anand, Amit

    2018-01-01

    Background Impaired response inhibition and poor impulse control are hallmarks of the manic phase of bipolar disorder but are also present during depressive and, to a lesser degree, euthymic periods. The neural mechanisms underlying these impairments are poorly understood, including how mechanisms are related to bipolar trait or state effects. Methods One-hundred four unmedicated participants with bipolar mania (BM) (n = 30), bipolar depression (BD) (n = 30), bipolar euthymia (BE) (n = 14), and healthy control subjects (n = 30) underwent functional magnetic resonance imaging during emotional and nonemotional go/no-go tasks. The go/no-go task requires participants to press a button for go stimuli, while inhibiting the response to no-go trials. In separate blocks, participants inhibited the response to happy faces, sad faces, or letters. Results The BE group had higher insula activity during happy face inhibition and greater activity in left inferior frontal gyrus during sad face inhibition, demonstrating bipolar trait effects. Relative to the BE group, BD and BM groups demonstrated lower insula activity during inhibition of happy faces, though the depressed sample had lower activity than manic patients. The BD and BM groups had a greater response to inhibiting sad faces in emotion processing and regulation regions, including putamen, insula, and lateral prefrontal cortex. The manic group also had higher activity in insula and putamen during neutral letter inhibition. Conclusions These results suggest distinct trait- and state-related neural abnormalities during response inhibition in bipolar disorder, with implications for future research and treatment. PMID:22871393

  14. Dynamic Encoding of Acoustic Features in Neural Responses to Continuous Speech.

    PubMed

    Khalighinejad, Bahar; Cruzatto da Silva, Guilherme; Mesgarani, Nima

    2017-02-22

    Humans are unique in their ability to communicate using spoken language. However, it remains unclear how the speech signal is transformed and represented in the brain at different stages of the auditory pathway. In this study, we characterized electroencephalography responses to continuous speech by obtaining the time-locked responses to phoneme instances (phoneme-related potential). We showed that responses to different phoneme categories are organized by phonetic features. We found that each instance of a phoneme in continuous speech produces multiple distinguishable neural responses occurring as early as 50 ms and as late as 400 ms after the phoneme onset. Comparing the patterns of phoneme similarity in the neural responses and the acoustic signals confirms a repetitive appearance of acoustic distinctions of phonemes in the neural data. Analysis of the phonetic and speaker information in neural activations revealed that different time intervals jointly encode the acoustic similarity of both phonetic and speaker categories. These findings provide evidence for a dynamic neural transformation of low-level speech features as they propagate along the auditory pathway, and form an empirical framework to study the representational changes in learning, attention, and speech disorders. SIGNIFICANCE STATEMENT We characterized the properties of evoked neural responses to phoneme instances in continuous speech. We show that each instance of a phoneme in continuous speech produces several observable neural responses at different times occurring as early as 50 ms and as late as 400 ms after the phoneme onset. Each temporal event explicitly encodes the acoustic similarity of phonemes, and linguistic and nonlinguistic information are best represented at different time intervals. Finally, we show a joint encoding of phonetic and speaker information, where the neural representation of speakers is dependent on phoneme category. These findings provide compelling new evidence for

  15. Advances in Cochlear Implant Telemetry: Evoked Neural Responses, Electrical Field Imaging, and Technical Integrity

    PubMed Central

    Mens, Lucas H. M.

    2007-01-01

    During the last decade, cochlear implantation has evolved into a well-established treatment of deafness, predominantly because of many improvements in speech processing and the controlled excitation of the auditory nerve. Cochlear implants now also feature telemetry, which is highly useful to monitor the proper functioning of the implanted electronics and electrode contacts. Telemetry can also support the clinical management in young children and difficult cases where neural unresponsiveness is suspected. This article will review recent advances in the telemetry of the electrically evoked compound action potential that have made these measurements simple and routine procedures in most cases. The distribution of the electrical stimulus itself sampled by “electrical field imaging” reveals general patterns of current flow in the normal cochlea and gross abnormalities in individual patients; models have been developed to derive more subtle insights from an individual electrical field imaging. Finally, some thoughts are given to the extended application of telemetry, for example, in monitoring the neural responses or in combination with other treatments of the deaf ear. PMID:17709572

  16. Neural signatures of cognitive and emotional biases in depression

    PubMed Central

    Fossati, Philippe

    2008-01-01

    Functional brain imaging studies suggest that depression is a system-level disorder affecting discrete but functionally linked cortical and limbic structures, with abnormalities in the anterior cingulate, lateral, ami medial prefrontal cortex, amygdala, ami hippocampus. Within this circuitry, abnormal corticolimbic interactions underlie cognitive deficits ami emotional impairment in depression. Depression involves biases toward processing negative emotional information and abnormal self-focus in response to emotional stimuli. These biases in depression could reflect excessive analytical self-focus in depression, as well as impaired cognitive control of emotional response to negative stimuli. By combining structural and functional investigations, brain imaging studies mav help to generate novel antidepressant treatments that regulate structural and factional plasticity within the neural network regulating mood and affective behavior.

  17. Abnormal neural activity of brain regions in treatment-resistant and treatment-sensitive major depressive disorder: a resting-state fMRI study.

    PubMed

    Guo, Wen-bin; Liu, Feng; Chen, Jin-dong; Gao, Keming; Xue, Zhi-min; Xu, Xi-jia; Wu, Ren-rong; Tan, Chang-lian; Sun, Xue-li; Liu, Zhe-ning; Chen, Hua-fu; Zhao, Jing-ping

    2012-10-01

    Patients with treatment-resistant depression (TRD) and those with treatment-sensitive depression (TSD) responded to antidepressants differently. Previous studies have commonly shown that patients with TRD or TSD had abnormal neural activity in different brain regions. In the present study, we used a coherence-based ReHo (Cohe-ReHo) approach to test the hypothesis that patients with TRD or TSD had abnormal neural activity in different brain regions. Twenty-three patients with TRD, 22 with TSD, and 19 healthy subjects (HS) matched with gender, age, and education level participated in the study. ANOVA analysis revealed widespread differences in Cohe-ReHo values among the three groups in different brain regions which included bilateral superior frontal gyrus, bilateral cerebellum, left inferior temporal gyrus, left occipital cortex, and both sides of fusiform gyrus. Compared to HS, lower Cohe-ReHo values were observed in TRD group in bilateral superior frontal gyrus and left cerebellum; in contrast, in TSD group, lower Cohe-ReHo values were mainly found in bilateral superior frontal gyrus. Compared to TSD group, TRD group had lower Cohe-ReHo in bilateral cerebellum and higher Cohe-ReHo in left fusiform gyrus. There was a negative correlation between Cohe-ReHo values of the left fusiform gyrus and illness duration in the pooled patients (r = 0.480, p = 0.001). The sensitivity and specificity of cerebellar Cohe-ReHo values differentiating TRD from TSD were 83% and 86%, respectively. Compared to healthy controls, both TRD and TSD patients shared the majority of brain regions with abnormal neural activity. However, the lower Cohe-ReHo values in the cerebellum might be as a marker to differentiate TRD from TSD with high sensitivity and specificity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Affective neural response to restricted interests in autism spectrum disorders.

    PubMed

    Cascio, Carissa J; Foss-Feig, Jennifer H; Heacock, Jessica; Schauder, Kimberly B; Loring, Whitney A; Rogers, Baxter P; Pryweller, Jennifer R; Newsom, Cassandra R; Cockhren, Jurnell; Cao, Aize; Bolton, Scott

    2014-01-01

    Restricted interests are a class of repetitive behavior in autism spectrum disorders (ASD) whose intensity and narrow focus often contribute to significant interference with daily functioning. While numerous neuroimaging studies have investigated executive circuits as putative neural substrates of repetitive behavior, recent work implicates affective neural circuits in restricted interests. We sought to explore the role of affective neural circuits and determine how restricted interests are distinguished from hobbies or interests in typical development. We compared a group of children with ASD to a typically developing (TD) group of children with strong interests or hobbies, employing parent report, an operant behavioral task, and functional imaging with personalized stimuli based on individual interests. While performance on the operant task was similar between the two groups, parent report of intensity and interference of interests was significantly higher in the ASD group. Both the ASD and TD groups showed increased BOLD response in widespread affective neural regions to the pictures of their own interest. When viewing pictures of other children's interests, the TD group showed a similar pattern, whereas BOLD response in the ASD group was much more limited. Increased BOLD response in the insula and anterior cingulate cortex distinguished the ASD from the TD group, and parent report of the intensity and interference with daily life of the child's restricted interest predicted insula response. While affective neural network response and operant behavior are comparable in typical and restricted interests, the narrowness of focus that clinically distinguishes restricted interests in ASD is reflected in more interference in daily life and aberrantly enhanced insula and anterior cingulate response to individuals' own interests in the ASD group. These results further support the involvement of affective neural networks in repetitive behaviors in ASD. © 2013 The

  19. Affective neural response to restricted interests in Autism Spectrum Disorders

    PubMed Central

    Cascio, Carissa J.; Foss-Feig, Jennifer H.; Heacock, Jessica; Schauder, Kimberly B.; Loring, Whitney A.; Rogers, Baxter P.; Pryweller, Jennifer R.; Newsom, Cassandra R.; Cockhren, Jurnell; Cao, Aize; Bolton, Scott

    2013-01-01

    Background Restricted interests are a class of repetitive behavior in autism spectrum disorders (ASD) whose intensity and narrow focus often contribute to significant interference with daily functioning. While numerous neuroimaging studies have investigated executive circuits as putative neural substrates of repetitive behavior, recent work implicates affective neural circuits in restricted interests. We sought to explore the role of affective neural circuits and determine how restricted interests are distinguished from hobbies or interests in typical development. Methods We compared a group of children with ASD to a typically developing (TD) group of children with strong interests or hobbies, employing parent report, an operant behavioral task, and functional imaging with personalized stimuli based on individual interests. Results While performance on the operant task was similar between the two groups, parent report of intensity and interference of interests was significantly higher in the ASD group. Both the ASD and TD groups showed increased BOLD response in widespread affective neural regions to pictures of their own interest. When viewing pictures of other children's interests, the TD group showed a similar pattern, whereas BOLD response in the ASD group was much more limited. Increased BOLD response in the insula and anterior cingulate cortex distinguished the ASD from the TD group, and parent report of the intensity and interference with daily life of the child's restricted interest predicted insula response. Conclusions While affective neural network response and operant behavior are comparable in typical and restricted interests, the narrowness of focus that clinically distinguishes restricted interests in ASD is reflected in more interference in daily life and aberrantly enhanced insula and anterior cingulate response to individuals’ own interests in the ASD group. These results further support the involvement of affective neural networks in repetitive

  20. Prediction and control of neural responses to pulsatile electrical stimulation

    NASA Astrophysics Data System (ADS)

    Campbell, Luke J.; Sly, David James; O'Leary, Stephen John

    2012-04-01

    This paper aims to predict and control the probability of firing of a neuron in response to pulsatile electrical stimulation of the type delivered by neural prostheses such as the cochlear implant, bionic eye or in deep brain stimulation. Using the cochlear implant as a model, we developed an efficient computational model that predicts the responses of auditory nerve fibers to electrical stimulation and evaluated the model's accuracy by comparing the model output with pooled responses from a group of guinea pig auditory nerve fibers. It was found that the model accurately predicted the changes in neural firing probability over time to constant and variable amplitude electrical pulse trains, including speech-derived signals, delivered at rates up to 889 pulses s-1. A simplified version of the model that did not incorporate adaptation was used to adaptively predict, within its limitations, the pulsatile electrical stimulus required to cause a desired response from neurons up to 250 pulses s-1. Future stimulation strategies for cochlear implants and other neural prostheses may be enhanced using similar models that account for the way that neural responses are altered by previous stimulation.

  1. Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction

    PubMed Central

    Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Parvaz, Muhammad A.; Alia-Klein, Nelly; Volkow, Nora D.; Goldstein, Rita Z.

    2012-01-01

    Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) which was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. PMID:22775285

  2. Abnormal Social Reward Responses in Anorexia Nervosa: An fMRI Study.

    PubMed

    Via, Esther; Soriano-Mas, Carles; Sánchez, Isabel; Forcano, Laura; Harrison, Ben J; Davey, Christopher G; Pujol, Jesús; Martínez-Zalacaín, Ignacio; Menchón, José M; Fernández-Aranda, Fernando; Cardoner, Narcís

    2015-01-01

    Patients with anorexia nervosa (AN) display impaired social interactions, implicated in the development and prognosis of the disorder. Importantly, social behavior is modulated by reward-based processes, and dysfunctional at-brain-level reward responses have been involved in AN neurobiological models. However, no prior evidence exists of whether these neural alterations would be equally present in social contexts. In this study, we conducted a cross-sectional social-judgment functional magnetic resonance imaging (fMRI) study of 20 restrictive-subtype AN patients and 20 matched healthy controls. Brain activity during acceptance and rejection was investigated and correlated with severity measures (Eating Disorder Inventory -EDI-2) and with personality traits of interest known to modulate social behavior (The Sensitivity to Punishment and Sensitivity to Reward Questionnaire). Patients showed hypoactivation of the dorsomedial prefrontal cortex (DMPFC) during social acceptance and hyperactivation of visual areas during social rejection. Ventral striatum activation during rejection was positively correlated in patients with clinical severity scores. During acceptance, activation of the frontal opercula-anterior insula and dorsomedial/dorsolateral prefrontal cortices was differentially associated with reward sensitivity between groups. These results suggest an abnormal motivational drive for social stimuli, and involve overlapping social cognition and reward systems leading to a disruption of adaptive responses in the processing of social reward. The specific association of reward-related regions with clinical and psychometric measures suggests the putative involvement of reward structures in the maintenance of pathological behaviors in AN.

  3. Functional neural networks underlying response inhibition in adolescents and adults.

    PubMed

    Stevens, Michael C; Kiehl, Kent A; Pearlson, Godfrey D; Calhoun, Vince D

    2007-07-19

    This study provides the first description of neural network dynamics associated with response inhibition in healthy adolescents and adults. Functional and effective connectivity analyses of whole brain hemodynamic activity elicited during performance of a Go/No-Go task were used to identify functionally integrated neural networks and characterize their causal interactions. Three response inhibition circuits formed a hierarchical, inter-dependent system wherein thalamic modulation of input to premotor cortex by fronto-striatal regions led to response suppression. Adolescents differed from adults in the degree of network engagement, regional fronto-striatal-thalamic connectivity, and network dynamics. We identify and characterize several age-related differences in the function of neural circuits that are associated with behavioral performance changes across adolescent development.

  4. The Variability of Neural Responses to Naturalistic Videos Change with Age and Sex.

    PubMed

    Petroni, Agustin; Cohen, Samantha S; Ai, Lei; Langer, Nicolas; Henin, Simon; Vanderwal, Tamara; Milham, Michael P; Parra, Lucas C

    2018-01-01

    Neural development is generally marked by an increase in the efficiency and diversity of neural processes. In a large sample ( n = 114) of human children and adults with ages ranging from 5 to 44 yr, we investigated the neural responses to naturalistic video stimuli. Videos from both real-life classroom settings and Hollywood feature films were used to probe different aspects of attention and engagement. For all stimuli, older ages were marked by more variable neural responses. Variability was assessed by the intersubject correlation of evoked electroencephalographic responses. Young males also had less-variable responses than young females. These results were replicated in an independent cohort ( n = 303). When interpreted in the context of neural maturation, we conclude that neural function becomes more variable with maturity, at least during the passive viewing of real-world stimuli.

  5. The Variability of Neural Responses to Naturalistic Videos Change with Age and Sex

    PubMed Central

    Petroni, Agustin; Langer, Nicolas; Milham, Michael P.

    2018-01-01

    Abstract Neural development is generally marked by an increase in the efficiency and diversity of neural processes. In a large sample (n = 114) of human children and adults with ages ranging from 5 to 44 yr, we investigated the neural responses to naturalistic video stimuli. Videos from both real-life classroom settings and Hollywood feature films were used to probe different aspects of attention and engagement. For all stimuli, older ages were marked by more variable neural responses. Variability was assessed by the intersubject correlation of evoked electroencephalographic responses. Young males also had less-variable responses than young females. These results were replicated in an independent cohort (n = 303). When interpreted in the context of neural maturation, we conclude that neural function becomes more variable with maturity, at least during the passive viewing of real-world stimuli. PMID:29379880

  6. Weak Responses to Auditory Feedback Perturbation during Articulation in Persons Who Stutter: Evidence for Abnormal Auditory-Motor Transformation

    PubMed Central

    Cai, Shanqing; Beal, Deryk S.; Ghosh, Satrajit S.; Tiede, Mark K.; Guenther, Frank H.; Perkell, Joseph S.

    2012-01-01

    Previous empirical observations have led researchers to propose that auditory feedback (the auditory perception of self-produced sounds when speaking) functions abnormally in the speech motor systems of persons who stutter (PWS). Researchers have theorized that an important neural basis of stuttering is the aberrant integration of auditory information into incipient speech motor commands. Because of the circumstantial support for these hypotheses and the differences and contradictions between them, there is a need for carefully designed experiments that directly examine auditory-motor integration during speech production in PWS. In the current study, we used real-time manipulation of auditory feedback to directly investigate whether the speech motor system of PWS utilizes auditory feedback abnormally during articulation and to characterize potential deficits of this auditory-motor integration. Twenty-one PWS and 18 fluent control participants were recruited. Using a short-latency formant-perturbation system, we examined participants’ compensatory responses to unanticipated perturbation of auditory feedback of the first formant frequency during the production of the monophthong [ε]. The PWS showed compensatory responses that were qualitatively similar to the controls’ and had close-to-normal latencies (∼150 ms), but the magnitudes of their responses were substantially and significantly smaller than those of the control participants (by 47% on average, p<0.05). Measurements of auditory acuity indicate that the weaker-than-normal compensatory responses in PWS were not attributable to a deficit in low-level auditory processing. These findings are consistent with the hypothesis that stuttering is associated with functional defects in the inverse models responsible for the transformation from the domain of auditory targets and auditory error information into the domain of speech motor commands. PMID:22911857

  7. Neurologic Correlates of Gait Abnormalities in Cerebral Palsy: Implications for Treatment

    PubMed Central

    Zhou, Joanne; Butler, Erin E.; Rose, Jessica

    2017-01-01

    Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP is often made based on abnormal muscle tone or posture, a delay in reaching motor milestones, or the presence of gait abnormalities in young children. Neuroimaging of high-risk neonates and of children diagnosed with CP have identified patterns of neurologic injury associated with CP, however, the neural underpinnings of common gait abnormalities remain largely uncharacterized. Here, we review the nature of the brain injury in CP, as well as the neuromuscular deficits and subsequent gait abnormalities common among children with CP. We first discuss brain injury in terms of mechanism, pattern, and time of injury during the prenatal, perinatal, or postnatal period in preterm and term-born children. Second, we outline neuromuscular deficits of CP with a focus on spastic CP, characterized by muscle weakness, shortened muscle-tendon unit, spasticity, and impaired selective motor control, on both a microscopic and functional level. Third, we examine the influence of neuromuscular deficits on gait abnormalities in CP, while considering emerging information on neural correlates of gait abnormalities and the implications for strategic treatment. This review of the neural basis of gait abnormalities in CP discusses what is known about links between the location and extent of brain injury and the type and severity of CP, in relation to the associated neuromuscular deficits, and subsequent gait abnormalities. Targeted treatment opportunities are identified that may improve functional outcomes for children with CP. By providing this context on the neural basis of gait abnormalities in CP, we hope to highlight areas of further research that can reduce the long-term, debilitating effects of CP. PMID:28367118

  8. Sub-meninges implantation reduces immune response to neural implants.

    PubMed

    Markwardt, Neil T; Stokol, Jodi; Rennaker, Robert L

    2013-04-15

    Glial scar formation around neural interfaces inhibits their ability to acquire usable signals from the surrounding neurons. To improve neural recording performance, the inflammatory response and glial scarring must be minimized. Previous work has indicated that meningeally derived cells participate in the immune response, and it is possible that the meninges may grow down around the shank of a neural implant, contributing to the formation of the glial scar. This study examines whether the glial scar can be reduced by placing a neural probe completely below the meninges. Rats were implanted with sets of loose microwire implants placed either completely below the meninges or implanted conventionally with the upper end penetrating the meninges, but not attached to the skull. Histological analysis was performed 4 weeks following surgical implantation to evaluate the glial scar. Our results found that sub-meninges implants showed an average reduction in reactive astrocyte activity of 63% compared to trans-meninges implants. Microglial activity was also reduced for sub-meninges implants. These results suggest that techniques that isolate implants from the meninges offer the potential to reduce the encapsulation response which should improve chronic recording quality and stability. Published by Elsevier B.V.

  9. Sub-meninges Implantation Reduces Immune Response to Neural Implants

    PubMed Central

    Markwardt, Neil T.; Stokol, Jodi; Rennaker, Robert L.

    2013-01-01

    Glial scar formation around neural interfaces inhibits their ability to acquire usable signals from the surrounding neurons. To improve neural recording performance, the inflammatory response and glial scarring must be minimized. Previous work has indicated that meningeally derived cells participate in the immune response, and it is possible that the meninges may grow down around the shank of a neural implant, contributing to the formation of the glial scar. This study examines whether the glial scar can be reduced by placing a neural probe completely below the meninges. Rats were implanted with sets of loose microwire implants placed either completely below the meninges or implanted conventionally with the upper end penetrating the meninges, but not attached to the skull. Histological analysis was performed 4 weeks following surgical implantation to evaluate the glial scar. Our results found that sub-meninges implants showed an average reduction in reactive astrocyte activity of 63% compared to trans-meninges implants. Microglial activity was also reduced for sub-meninges implants. These results suggest that techniques that isolate implants from the meninges offer the potential to reduce the encapsulation response which should improve chronic recording quality and stability. PMID:23370311

  10. Genetically induced abnormal cranial development in human trisomy 18 with holoprosencephaly: comparisons with the normal tempo of osteogenic-neural development.

    PubMed

    Reid, Shaina N; Ziermann, Janine M; Gondré-Lewis, Marjorie C

    2015-07-01

    Craniofacial malformations are common congenital defects caused by failed midline inductive signals. These midline defects are associated with exposure of the fetus to exogenous teratogens and with inborn genetic errors such as those found in Down, Patau, Edwards' and Smith-Lemli-Opitz syndromes. Yet, there are no studies that analyze contributions of synchronous neurocranial and neural development in these disorders. Here we present the first in-depth analysis of malformations of the basicranium of a holoprosencephalic (HPE) trisomy 18 (T18; Edwards' syndrome) fetus with synophthalmic cyclopia and alobar HPE. With a combination of traditional gross dissection and state-of-the-art computed tomography, we demonstrate the deleterious effects of T18 caused by a translocation at 18p11.31. Bony features included a single developmentally unseparated frontal bone, and complete dual absence of the anterior cranial fossa and ethmoid bone. From a superior view with the calvarium plates removed, there was direct visual access to the orbital foramen and hard palate. Both the eyes and the pituitary gland, normally protected by bony structures, were exposed in the cranial cavity and in direct contact with the brain. The middle cranial fossa was shifted anteriorly, and foramina were either missing or displaced to an abnormal location due to the absence or misplacement of its respective cranial nerve (CN). When CN development was conserved in its induction and placement, the respective foramen developed in its normal location albeit with abnormal gross anatomical features, as seen in the facial nerve (CNVII) and the internal acoustic meatus. More anteriorly localized CNs and their foramina were absent or heavily disrupted compared with posterior ones. The severe malformations exhibited in the cranial fossae, orbital region, pituitary gland and sella turcica highlight the crucial involvement of transcription factors such as TGIF, which is located on chromosome 18 and contributes

  11. Abnormal medial prefrontal cortex activity in heavy cannabis users during conscious emotional evaluation.

    PubMed

    Wesley, Michael J; Lile, Joshua A; Hanlon, Colleen A; Porrino, Linda J

    2016-03-01

    Long-term heavy cannabis users (cannabis users) who are not acutely intoxicated have diminished subconscious neural responsiveness to affective stimuli. This study sought to determine if abnormal processing extends to the conscious evaluation of emotional stimuli. Functional magnetic resonance imaging (fMRI) was used to examine brain activity as cannabis users (N = 16) and non-cannabis-using controls (N = 17) evaluated and categorized standardized International Affective Picture System (IAPS) stimuli. Individual judgments were used to isolate activity during the evaluation of emotional (i.e., emotional evaluation) or neutral (i.e., neutral evaluation) stimuli. Within- and between-group analyses were performed. Both groups judged the same stimuli as emotional and had activations in visual, midbrain, and middle cingulate cortices during emotional evaluation, relative to neutral. Within-group analyses also revealed amygdalar and inferior frontal gyrus activations in controls, but not cannabis users, and medial prefrontal cortex (mPFC) deactivations in cannabis users, but not controls, during emotional evaluation, relative to neutral. Between-group comparisons found that mPFC activity during positive and negative evaluation was significantly hypoactive in cannabis users, relative to controls. Abnormal neural processing of affective content extends to the level of consciousness in cannabis users. The hypoactive mPFC responses observed resembles the attenuated mPFC responses found during increased non-affective cognitive load in prior research. These findings suggest that abnormal mPFC singling in cannabis users during emotional evaluation might be associated with increased non-affective cognitive load.

  12. Diminished neural responses predict enhanced intrinsic motivation and sensitivity to external incentive.

    PubMed

    Marsden, Karen E; Ma, Wei Ji; Deci, Edward L; Ryan, Richard M; Chiu, Pearl H

    2015-06-01

    The duration and quality of human performance depend on both intrinsic motivation and external incentives. However, little is known about the neuroscientific basis of this interplay between internal and external motivators. Here, we used functional magnetic resonance imaging to examine the neural substrates of intrinsic motivation, operationalized as the free-choice time spent on a task when this was not required, and tested the neural and behavioral effects of external reward on intrinsic motivation. We found that increased duration of free-choice time was predicted by generally diminished neural responses in regions associated with cognitive and affective regulation. By comparison, the possibility of additional reward improved task accuracy, and specifically increased neural and behavioral responses following errors. Those individuals with the smallest neural responses associated with intrinsic motivation exhibited the greatest error-related neural enhancement under the external contingency of possible reward. Together, these data suggest that human performance is guided by a "tonic" and "phasic" relationship between the neural substrates of intrinsic motivation (tonic) and the impact of external incentives (phasic).

  13. Functional neural networks underlying response inhibition in adolescents and adults

    PubMed Central

    Stevens, Michael C.; Kiehl, Kent A.; Pearlson, Godfrey D.; Calhoun, Vince D.

    2008-01-01

    This study provides the first description of neural network dynamics associated with response inhibition in healthy adolescents and adults. Functional and effective connectivity analyses of whole brain hemodynamic activity elicited during performance of a Go/No-Go task were used to identify functionally-integrated neural networks and characterize their causal interactions. Three response inhibition circuits formed a hierarchical, inter-dependent system wherein thalamic modulation of input to premotor cortex by frontostriatal regions led to response suppression. Adolescents differed from adults in the degree of network engagement, regional fronto-striatal-thalamic connectivity, and network dynamics. We identify and characterize several age-related differences in the function of neural circuits that are associated with behavioral performance changes across adolescent development. PMID:17467816

  14. Common and disorder-specific neural responses to emotional faces in generalised anxiety, social anxiety and panic disorders

    PubMed Central

    Fonzo, Gregory A.; Ramsawh, Holly J.; Flagan, Taru M.; Sullivan, Sarah G.; Letamendi, Andrea; Simmons, Alan N.; Paulus, Martin P.; Stein, Murray B.

    2015-01-01

    Background Although evidence exists for abnormal brain function across various anxiety disorders, direct comparison of neural function across diagnoses is needed to elicit abnormalities common across disorders and those distinct to a particular diagnosis. Aims To delineate common and distinct abnormalities within generalised anxiety (GAD), panic and social anxiety disorder (SAD) during affective processing. Method Fifty-nine adults (15 with GAD, 15 with panic disorder, 14 with SAD, and 15 healthy controls) underwent functional magnetic resonance imaging while completing a facial emotion matching task with fearful, angry and happy faces. Results Greater differential right amygdala activation to matching fearful v. happy facial expressions related to greater negative affectivity (i.e. trait anxiety) and was heightened across all anxiety disorder groups compared with controls. Collapsing across emotional face types, participants with panic disorder uniquely displayed greater posterior insula activation. Conclusions These preliminary results highlight a common neural basis for clinical anxiety in these diagnoses and also suggest the presence of disorder-specific dysfunction. PMID:25573399

  15. Oxytocin modulates the racial bias in neural responses to others' suffering.

    PubMed

    Sheng, Feng; Liu, Yi; Zhou, Bin; Zhou, Wen; Han, Shihui

    2013-02-01

    The intergroup relationship between a perceiver and a target person influences empathic neural responses to others' suffering, which are increased for racial in-group members compared to out-group members. The current study investigated whether oxytocin (OT), a neuropeptide that has been linked to empathic concern and in-group favoritism, contributes to the racial bias in empathic neural responses. Event-related brain potentials were recorded in Chinese male adults during race judgments on Asian and Caucasian faces expressing pain or showing a neutral expression after intranasal self-administration of OT or placebo. A fronto-central positive activity at 128-188 ms (P2) was of larger amplitude in response to the pain expressions compared with the neutral expressions of racial in-group members but not of racial out-group members. OT treatment increased this racial in-group bias in neural responses and resulted in its correlation with a positive implicit attitude toward racial in-group members. Our findings suggest that OT interacts with the intergroup relationship to modulate empathic neural responses to others' suffering. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Ectopic Expression of Nolz-1 in Neural Progenitors Promotes Cell Cycle Exit/Premature Neuronal Differentiation Accompanying with Abnormal Apoptosis in the Developing Mouse Telencephalon

    PubMed Central

    Chang, Sunny Li-Yun; Chen, Shih-Yun; Huang, Huai-Huei; Ko, Hsin-An; Liu, Pei-Tsen; Liu, Ya-Chi; Chen, Ping-Hau; Liu, Fu-Chin

    2013-01-01

    Nolz-1, as a murine member of the NET zinc-finger protein family, is expressed in post-mitotic differentiating neurons of striatum during development. To explore the function of Nolz-1 in regulating the neurogenesis of forebrain, we studied the effects of ectopic expression of Nolz-1 in neural progenitors. We generated the Cre-loxP dependent conditional transgenic mice in which Nolz-1 was ectopically expressed in proliferative neural progenitors. Ectopic expression of Nolz-1 in neural progenitors by intercrossing the Nolz-1 conditional transgenic mice with the nestin-Cre mice resulted in hypoplasia of telencephalon in double transgenic mice. Decreased proliferation of neural progenitor cells were found in the telencephalon, as evidenced by the reduction of BrdU−, Ki67− and phospho-histone 3-positive cells in E11.5–12.5 germinal zone of telencephalon. Transgenic Nolz-1 also promoted cell cycle exit and as a consequence might facilitate premature differentiation of progenitors, because TuJ1-positive neurons were ectopically found in the ventricular zone and there was a general increase of TuJ1 immunoreactivity in the telencephalon. Moreover, clusters of strong TuJ1-expressing neurons were present in E12.5 germinal zone. Some of these strong TuJ1-positive clusters, however, contained apoptotic condensed DNA, suggesting that inappropriate premature differentiation may lead to abnormal apoptosis in some progenitor cells. Consistent with the transgenic mouse analysis in vivo, similar effects of Nozl-1 over-expression in induction of apoptosis, inhibition of cell proliferation and promotion of neuronal differentiation were also observed in three different N18, ST14A and N2A neural cell lines in vitro. Taken together, our study indicates that ectopic expression of Nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation and induces abnormal apoptosis in the developing telencephalon. PMID:24073229

  17. Ectopic expression of nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation accompanying with abnormal apoptosis in the developing mouse telencephalon.

    PubMed

    Chang, Sunny Li-Yun; Chen, Shih-Yun; Huang, Huai-Huei; Ko, Hsin-An; Liu, Pei-Tsen; Liu, Ya-Chi; Chen, Ping-Hau; Liu, Fu-Chin

    2013-01-01

    Nolz-1, as a murine member of the NET zinc-finger protein family, is expressed in post-mitotic differentiating neurons of striatum during development. To explore the function of Nolz-1 in regulating the neurogenesis of forebrain, we studied the effects of ectopic expression of Nolz-1 in neural progenitors. We generated the Cre-loxP dependent conditional transgenic mice in which Nolz-1 was ectopically expressed in proliferative neural progenitors. Ectopic expression of Nolz-1 in neural progenitors by intercrossing the Nolz-1 conditional transgenic mice with the nestin-Cre mice resulted in hypoplasia of telencephalon in double transgenic mice. Decreased proliferation of neural progenitor cells were found in the telencephalon, as evidenced by the reduction of BrdU-, Ki67- and phospho-histone 3-positive cells in E11.5-12.5 germinal zone of telencephalon. Transgenic Nolz-1 also promoted cell cycle exit and as a consequence might facilitate premature differentiation of progenitors, because TuJ1-positive neurons were ectopically found in the ventricular zone and there was a general increase of TuJ1 immunoreactivity in the telencephalon. Moreover, clusters of strong TuJ1-expressing neurons were present in E12.5 germinal zone. Some of these strong TuJ1-positive clusters, however, contained apoptotic condensed DNA, suggesting that inappropriate premature differentiation may lead to abnormal apoptosis in some progenitor cells. Consistent with the transgenic mouse analysis in vivo, similar effects of Nozl-1 over-expression in induction of apoptosis, inhibition of cell proliferation and promotion of neuronal differentiation were also observed in three different N18, ST14A and N2A neural cell lines in vitro. Taken together, our study indicates that ectopic expression of Nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation and induces abnormal apoptosis in the developing telencephalon.

  18. Balancing uncertainty and acceptance: understanding Chinese women's responses to an abnormal cervical smear result.

    PubMed

    Twinn, Sheila

    2006-09-01

    The aims of this study were to examine the responses of Hong Kong Chinese women receiving an abnormal smear result and to compare any differences in responses depending on the diagnosis of the abnormal smear. The implementation of cervical screening programmes has resulted in an increasing number of women receiving an abnormal smear result requiring cytological surveillance or referral for colposcopy. Evidence suggests that women frequently misunderstood such results, believing that they already have cancer. However, little is known about the responses of Chinese women in this situation. An exploratory qualitative study. Face-to-face semi-structured tape-recorded interviews were undertaken with 66 women sampled opportunistically from an urban centre of a major non-governmental service provider. Amongst this sample, 22 women required cytological surveillance, 20 required treatment for vaginitis and 24 were referred for colposcopy. Thematic analysis was undertaken of the translated interviews within and across groups to identify categories and themes illustrating women's responses to an abnormal smear result. An important difference in the comparison of the data sets was that of women's understanding of the cause of the abnormal result. Women with vaginitis understood the cause of their abnormality, whereas those in the other groups remained unclear about their abnormality, generating feelings of fear and uncertainty. Trust in practitioners influenced women's acceptance of the result. Although responses of Chinese women are similar to those in other population groups, with those referred for colposcopy experiencing greater anxiety than those undergoing cytological surveillance, balancing feelings of uncertainty and acceptance influenced Chinese women's responses to their abnormal results and allowed them to make sense of their result in their everyday life. Trust in the practitioner was essential to the acceptance of their result. Such findings highlight implications

  19. Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction.

    PubMed

    Konova, Anna B; Moeller, Scott J; Tomasi, Dardo; Parvaz, Muhammad A; Alia-Klein, Nelly; Volkow, Nora D; Goldstein, Rita Z

    2012-10-01

    Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie the maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) that was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both the function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. © 2012 Published 2012. This article is a US Government work and is in the public domain in the USA.

  20. Neural responses to macronutrients: hedonic and homeostatic mechanisms.

    PubMed

    Tulloch, Alastair J; Murray, Susan; Vaicekonyte, Regina; Avena, Nicole M

    2015-05-01

    The brain responds to macronutrients via intricate mechanisms. We review how the brain's neural systems implicated in homeostatic control of feeding and hedonic responses are influenced by the ingestion of specific types of food. We discuss how these neural systems are dysregulated in preclinical models of obesity. Findings from these studies can increase our understanding of overeating and, perhaps in some cases, the development of obesity. In addition, a greater understanding of the neural circuits affected by the consumption of specific macronutrients, and by obesity, might lead to new treatments and strategies for preventing unhealthy weight gain. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. Identification of Abnormal System Noise Temperature Patterns in Deep Space Network Antennas Using Neural Network Trained Fuzzy Logic

    NASA Technical Reports Server (NTRS)

    Lu, Thomas; Pham, Timothy; Liao, Jason

    2011-01-01

    This paper presents the development of a fuzzy logic function trained by an artificial neural network to classify the system noise temperature (SNT) of antennas in the NASA Deep Space Network (DSN). The SNT data were classified into normal, marginal, and abnormal classes. The irregular SNT pattern was further correlated with link margin and weather data. A reasonably good correlation is detected among high SNT, low link margin and the effect of bad weather; however we also saw some unexpected non-correlations which merit further study in the future.

  2. Abnormal Medial Prefrontal Cortex Activity in Heavy Cannabis Users During Conscious Emotional Evaluation

    PubMed Central

    Lile, Joshua A.; Hanlon, Colleen A.; Porrino, Linda J.

    2015-01-01

    Rationale Long-term heavy cannabis users (cannabis users) who are not acutely intoxicated have diminished subconscious neural responsiveness to affective stimuli. Objective This study sought to determine if abnormal processing extends to the conscious evaluation of emotional stimuli. Methods Functional Magnetic Resonance Imaging (fMRI) was used to examine brain activity as cannabis users (N=16) and non-cannabis using controls (N=17) evaluated and categorized standardized International Affective Picture System (IAPS) stimuli. Individual judgments were used to isolate activity during the evaluation of emotional (i.e., emotional evaluation) or neutral (i.e., neutral evaluation) stimuli. Within- and between-group analyses were performed. Results Both groups judged the same stimuli as emotional and had activations in visual, midbrain, and middle cingulate cortices during emotional evaluation, relative to neutral. Within-group analyses also revealed amygdalar and inferior frontal gyrus activations in controls, but not cannabis users, and medial prefrontal cortex (mPFC) deactivations in cannabis users, but not controls, during emotional evaluation, relative to neutral. Between-group comparisons found that mPFC activity during positive and negative evaluation was significantly hypoactive in cannabis users, relative to controls. Conclusions Abnormal neural processing of affective content extends to the level of consciousness in cannabis users. The hypoactive mPFC responses observed resembles the attenuated mPFC responses found during increased non-affective cognitive load in prior research. These findings suggest that abnormal mPFC singling in cannabis users during emotional evaluation might be associated with increased non-affective cognitive load. PMID:26690589

  3. Degraded neural and behavioral processing of speech sounds in a rat model of Rett syndrome

    PubMed Central

    Engineer, Crystal T.; Rahebi, Kimiya C.; Borland, Michael S.; Buell, Elizabeth P.; Centanni, Tracy M.; Fink, Melyssa K.; Im, Kwok W.; Wilson, Linda G.; Kilgard, Michael P.

    2015-01-01

    Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal. In this study, we used the novel rat Mecp2 knockout model of Rett syndrome to document the neural and behavioral processing of speech sounds. We hypothesized that both speech discrimination ability and the neural response to speech sounds would be impaired in Mecp2 rats. We expected that extensive speech training would improve speech discrimination ability and the cortical response to speech sounds. Our results reveal that speech responses across all four auditory cortex fields of Mecp2 rats were hyperexcitable, responded slower, and were less able to follow rapidly presented sounds. While Mecp2 rats could accurately perform consonant and vowel discrimination tasks in quiet, they were significantly impaired at speech sound discrimination in background noise. Extensive speech training improved discrimination ability. Training shifted cortical responses in both Mecp2 and control rats to favor the onset of speech sounds. While training increased the response to low frequency sounds in control rats, the opposite occurred in Mecp2 rats. Although neural coding and plasticity are abnormal in the rat model of Rett syndrome, extensive therapy appears to be effective. These findings may help to explain some aspects of communication deficits in Rett syndrome and suggest that extensive rehabilitation therapy might prove beneficial. PMID:26321676

  4. Abnormal IgG4 antibody response to aeroallergens in allergic patients.

    PubMed

    Jeannin, P; Delneste, Y; Tillie-Leblond, I; Wallaert, B; carlier, A; Pestel, J; Tonnel, A B

    1994-01-01

    Various studies have suggested the involvement of immunoglobulin G4 (IgG4) antibodies (Ab) in the physiopathology of allergic disorders. Recently, an abnormal IgG4 Ab production in response to immunization has been reported in some atopic patients. Thus, in order to evidence in allergic patients, a potential abnormal IgG4 Ab response to aeroallergens following natural exposure, we compared, in 34 patients sensitive to Dermatophagoides pteronyssinus and in 16 healthy subjects, the IgG4 Ab response to D. pteronyssinus, grass pollen and cat dander, using a solid-phase radioimmunoassay. Since some patients were also sensitive to grass pollen and/or to cat dander, we analyzed, in all patients, the IgG4 Ab responses both towards the allergen(s) they were sensitive to (sensitizing allergen) or not (unrelated allergen). The results showed that 90% of the patients produced levels of antisensitizing allergen(s) IgG4 Ab significantly higher than the controls; this IgG4 Ab response was correlated with the corresponding specific IgE Ab level. In addition, among these patients, around 40% presented high levels of IgG4 Ab to the unrelated allergen(s). Thus, in allergic patients, while specific IgE Ab define the nature of the sensitizing allergen, the presence of IgG4 Ab directed against various allergens seems in relation with an abnormal isotype regulation associated with atopic disorders.

  5. Amygdala abnormalities in first-degree relatives of individuals with schizophrenia unmasked by benzodiazepine challenge

    PubMed Central

    Wolf, Daniel H.; Satterthwaite, Theodore D.; Loughead, James; Pinkham, Amy; Overton, Eve; Elliott, Mark A.; Dent, Gersham W.; Smith, Mark A.; Gur, Ruben C.; Gur, Raquel E.

    2014-01-01

    Rationale Impaired emotion processing in schizophrenia predicts broader social dysfunction and has been related to negative symptom severity and amygdala dysfunction. Pharmacological modulation of emotion-processing deficits and related neural abnormalities may provide useful phenotypes for pathophysiological investigation. Objectives We used an acute benzodiazepine challenge to identify and modulate potential emotion-processing abnormalities in 20 unaffected first-degree relatives of individuals with schizophrenia, compared to 25 control subjects without a family history of psychosis. Methods An oral 1mg dose of the short-acting anxiolytic benzodiazepine alprazolam was administered in a balanced crossover placebo-controlled double-blind design, preceding identical 3T fMRI sessions approximately 1 week apart. Primary outcomes included fMRI activity in amygdala and related regions during two facial emotion-processing tasks: emotion identification and emotion memory. Results Family members exhibited abnormally strong alprazolam-induced reduction in amygdala and hippocampus activation during emotion identification, compared to equal reduction in both groups for the emotion memory task. Conclusions GABAergic modulation with alprazolam produced differential responses in family members vs. controls, perhaps by unmasking underlying amygdalar and/or GABAergic abnormalities. Such pharmacological fMRI paradigms could prove useful for developing drugs targeting specific neural circuits to treat or prevent schizophrenia. PMID:21603892

  6. Shared beliefs enhance shared feelings: religious/irreligious identifications modulate empathic neural responses.

    PubMed

    Huang, Siyuan; Han, Shihui

    2014-01-01

    Recent neuroimaging research has revealed stronger empathic neural responses to same-race compared to other-race individuals. Is the in-group favouritism in empathic neural responses specific to race identification or a more general effect of social identification-including those based on religious/irreligious beliefs? The present study investigated whether and how intergroup relationships based on religious/irreligious identifications modulate empathic neural responses to others' pain expressions. We recorded event-related brain potentials from Chinese Christian and atheist participants while they perceived pain or neutral expressions of Chinese faces that were marked as being Christians or atheists. We found that both Christian and atheist participants showed stronger neural activity to pain (versus neutral) expressions at 132-168 ms and 200-320 ms over the frontal region to those with the same (versus different) religious/irreligious beliefs. The in-group favouritism in empathic neural responses was also evident in a later time window (412-612 ms) over the central/parietal regions in Christian but not in atheist participants. Our results indicate that the intergroup relationship based on shared beliefs, either religious or irreligious, can lead to in-group favouritism in empathy for others' suffering.

  7. Abnormalities of neural circuitry in Alzheimer's disease: hippocampus and cortical cholinergic innervation.

    PubMed

    Geula, C

    1998-07-01

    Severe pathology in Alzheimer's disease (AD) results in marked disruption of cortical circuitry. Formation of neurofibrillary tangles, neuronal loss, decrease in dendritic extent, and synaptic depletion combine to halt communication among various cortical areas, resulting in anatomic isolation and fragmentation of many cortical zones. The clinical manifestation of this disruption is severe and debilitating cognitive dysfunction, often accompanied by psychiatric and behavioral disturbances and a diminished ability to perform activities of daily living. However, different cortical circuits are not equally vulnerable to AD pathology. In particular, two cortical systems that appear to be involved in the neural processing of memory are selectively vulnerable to degeneration in AD. One consists of connections between the hippocampus and its neighboring cortical structures within the temporal lobe. The second is the cortical cholinergic system that originates in neurons within the basal forebrain and innervates the entire cortical mantle. The circuitry in these systems shows early and severe degenerative changes in the course of AD. The selective vulnerability of these circuits is the probable reason for the early and marked loss of memory observed in these patients. This review presents current knowledge of the general pattern of cortical circuitry, followed by a summary of abnormalities of this circuitry in AD. The cortical circuits that exhibit selective pathology in AD are described in greater detail. Therapeutic implications of the abnormal circuitry in AD are also discussed. For therapies to be effective, early diagnosis of AD is necessary. Future efforts at AD therapy must be combined with an equally intense effort to develop tools capable of early diagnosis of AD, preferably at a preclinical stage before the onset of cognitive symptoms.

  8. Gamma-band abnormalities as markers of autism spectrum disorders

    PubMed Central

    Rojas, Donald C.; Wilson, Lisa B.

    2014-01-01

    Summary Autism is a behaviorally diagnosed neurodevelopmental disorder with no current biomarkers with high specificity and sensitivity. Gamma-band abnormalities have been reported in many studies of autism spectrum disorders. Gamma-band activity is associated with perceptual and cognitive functions that are compromised in autism. Some gamma-band deficits have also been seen in unaffected first-degree relatives, suggesting heritability of these findings. This review covers the published literature on gamma abnormalities in autism, the proposed mechanisms underlying the deficits, and the potential for translation into new treatments. Although the utility of gamma-band metrics as diagnostic biomarkers is currently limited, such changes in autism are also useful as endophenotypes, for evaluating potential neural mechanisms, and for use as surrogate markers of treatment response to interventions. PMID:24712425

  9. Acute D3 Antagonist GSK598809 Selectively Enhances Neural Response During Monetary Reward Anticipation in Drug and Alcohol Dependence

    PubMed Central

    Murphy, Anna; Nestor, Liam J; McGonigle, John; Paterson, Louise; Boyapati, Venkataramana; Ersche, Karen D; Flechais, Remy; Kuchibatla, Shankar; Metastasio, Antonio; Orban, Csaba; Passetti, Filippo; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor; Robbins, Trevor W; Lingford-Hughes, Anne; Nutt, David J; Deakin, John FW; Elliott, Rebecca

    2017-01-01

    Evidence suggests that disturbances in neurobiological mechanisms of reward and inhibitory control maintain addiction and provoke relapse during abstinence. Abnormalities within the dopamine system may contribute to these disturbances and pharmacologically targeting the D3 dopamine receptor (DRD3) is therefore of significant clinical interest. We used functional magnetic resonance imaging to investigate the acute effects of the DRD3 antagonist GSK598809 on anticipatory reward processing, using the monetary incentive delay task (MIDT), and response inhibition using the Go/No-Go task (GNGT). A double-blind, placebo-controlled, crossover design approach was used in abstinent alcohol dependent, abstinent poly-drug dependent and healthy control volunteers. For the MIDT, there was evidence of blunted ventral striatal response to reward in the poly-drug-dependent group under placebo. GSK598809 normalized ventral striatal reward response and enhanced response in the DRD3-rich regions of the ventral pallidum and substantia nigra. Exploratory investigations suggested that the effects of GSK598809 were mainly driven by those with primary dependence on alcohol but not on opiates. Taken together, these findings suggest that GSK598809 may remediate reward deficits in substance dependence. For the GNGT, enhanced response in the inferior frontal cortex of the poly-drug group was found. However, there were no effects of GSK598809 on the neural network underlying response inhibition nor were there any behavioral drug effects on response inhibition. GSK598809 modulated the neural network underlying reward anticipation but not response inhibition, suggesting that DRD3 antagonists may restore reward deficits in addiction. PMID:28042871

  10. Response variance in functional maps: neural darwinism revisited.

    PubMed

    Takahashi, Hirokazu; Yokota, Ryo; Kanzaki, Ryohei

    2013-01-01

    The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population.

  11. Response Variance in Functional Maps: Neural Darwinism Revisited

    PubMed Central

    Takahashi, Hirokazu; Yokota, Ryo; Kanzaki, Ryohei

    2013-01-01

    The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population. PMID:23874733

  12. Response of neural reward regions to food cues in autism spectrum disorders

    PubMed Central

    2012-01-01

    Background One hypothesis for the social deficits that characterize autism spectrum disorders (ASD) is diminished neural reward response to social interaction and attachment. Prior research using established monetary reward paradigms as a test of non-social reward to compare with social reward may involve confounds in the ability of individuals with ASD to utilize symbolic representation of money and the abstraction required to interpret monetary gains. Thus, a useful addition to our understanding of neural reward circuitry in ASD includes a characterization of the neural response to primary rewards. Method We asked 17 children with ASD and 18 children without ASD to abstain from eating for at least four hours before an MRI scan in which they viewed images of high-calorie foods. We assessed the neural reward network for increases in the blood oxygenation level dependent (BOLD) signal in response to the food images Results We found very similar patterns of increased BOLD signal to these images in the two groups; both groups showed increased BOLD signal in the bilateral amygdala, as well as in the nucleus accumbens, orbitofrontal cortex, and insula. Direct group comparisons revealed that the ASD group showed a stronger response to food cues in bilateral insula along the anterior-posterior gradient and in the anterior cingulate cortex than the control group, whereas there were no neural reward regions that showed higher activation for controls than for ASD. Conclusion These results suggest that neural response to primary rewards is not diminished but in fact shows an aberrant enhancement in children with ASD. PMID:22958533

  13. Visual development in primates: Neural mechanisms and critical periods

    PubMed Central

    Kiorpes, Lynne

    2015-01-01

    Despite many decades of research into the development of visual cortex, it remains unclear what neural processes set limitations on the development of visual function and define its vulnerability to abnormal visual experience. This selected review examines the development of visual function and its neural correlates, and highlights the fact that in most cases receptive field properties of infant neurons are substantially more mature than infant visual function. One exception is temporal resolution, which can be accounted for by resolution of neurons at the level of the LGN. In terms of spatial vision, properties of single neurons alone are not sufficient to account for visual development. Different visual functions develop over different time courses. Their onset may be limited by the existence of neural response properties that support a given perceptual ability, but the subsequent time course of maturation to adult levels remains unexplained. Several examples are offered suggesting that taking account of weak signaling by infant neurons, correlated firing, and pooled responses of populations of neurons brings us closer to an understanding of the relationship between neural and behavioral development. PMID:25649764

  14. Proportionate Responses to Life Events Influence Clinicians’ Judgments Of Psychological Abnormality

    PubMed Central

    Kim, Nancy S.; Paulus, Daniel J.; Gonzalez, Jeffrey S.; Khalife, Danielle

    2012-01-01

    Psychological abnormality is a fundamental concept in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR; APA, 2000) and in all clinical evaluations. How do practicing clinical psychologists use the context of life events to judge the abnormality of a person’s current behaviors? The appropriate role of life-event context in assessment has long been the subject of intense debate and scrutiny among clinical theorists, yet relatively little is known about clinicians’ own judgments in practice. We propose a proportionate-response hypothesis, such that judgments of abnormality are influenced by whether the behaviors are a disproportionate response to past events, rendering them difficult to understand or explain. We presented licensed, practicing clinical psychologists (N=77) with vignettes describing hypothetical people’s behaviors (disordered, mildly distressed, or unaffected) that had been preceded by either traumatic or mildly distressing events. Experts’ judgments of abnormality were strongly and systematically influenced by the degree of mismatch between the past event and current behaviors in strength and valence, such that the greater the mismatch, the more abnormal the person seemed. A separate, additional group of clinical psychologists (N=20) further confirmed that the greater the degree of mismatch, the greater the perceived difficulty in understanding the patient. These findings held true across clinicians of different theoretical orientations and in disorders for which these patterns of judgments ran contrary to formal recommendations in the DSM-IV-TR (APA, 2000). The rationality of these effects and implications for clinical decision science are discussed. PMID:22142425

  15. The nurse response to abnormal vital sign recording in the emergency department.

    PubMed

    Johnson, Kimberly D; Mueller, Lindsey; Winkelman, Chris

    2017-01-01

    To examine what occurs after a recorded observation of at least one abnormal vital sign in the emergency department. The aims were to determine how often abnormal vital signs were recorded, what interventions were documented, and what factors were associated with documented follow-up for abnormal vital signs. Monitoring quality of care, and preventing or intervening before harm occurs to patients are central to nurses' roles. Abnormal vital signs have been associated with poor patient outcomes and require follow-up after the observation of abnormal readings to prevent patient harm related to a deteriorating status. This documentation is important to quality and safety of care. Observational, retrospective chart review. Modified Early Warning Score was calculated for all recorded vital signs for 195 charts. Comparisons were made between groups: (1) no abnormal vital signs, (2) abnormal vital sign present, but normal Modified Early Warning Score and (3) critically abnormal Modified Early Warning Score. About 62·1% of charts had an abnormal vital sign documented. Critically abnormal values were present in 14·9%. No documentation was present in 44·6% of abnormal cases. When interventions were documented, it was usually to notify the physician. The timing within the emergency department visit when the abnormalities were observed and the degree of abnormality had significant relationships to the presence of documentation. It is doubtful that nurses do not recognise abnormalities because more severely abnormal vital signs were more likely to have documented follow-up. Perhaps the interruptive nature of the emergency department or the prioritised actions of the nurse impacted documentation within this study. Further research is required to determine why follow-up is not being documented. To ensure safety and quality of patient care, accurate documentation of responses to abnormal vital signs is required. © 2016 John Wiley & Sons Ltd.

  16. Young Adult Smokers' Neural Response to Graphic Cigarette Warning Labels.

    PubMed

    Green, Adam E; Mays, Darren; Falk, Emily B; Vallone, Donna; Gallagher, Natalie; Richardson, Amanda; Tercyak, Kenneth P; Abrams, David B; Niaura, Raymond S

    2016-06-01

    The study examined young adult smokers' neural response to graphic warning labels (GWLs) on cigarette packs using functional magnetic resonance imaging (fMRI). Nineteen young adult smokers ( M age 22.9, 52.6% male, 68.4% non-white, M 4.3 cigarettes/day) completed pre-scan, self-report measures of demographics, cigarette smoking behavior, and nicotine dependence, and an fMRI scanning session. During the scanning session participants viewed cigarette pack images (total 64 stimuli, viewed 4 seconds each) that varied based on the warning label (graphic or visually occluded control) and pack branding (branded or plain packaging) in an event-related experimental design. Participants reported motivation to quit (MTQ) in response to each image using a push-button control. Whole-brain blood oxygenation level-dependent (BOLD) functional images were acquired during the task. GWLs produced significantly greater self-reported MTQ than control warnings ( p < .001). Imaging data indicate stronger neural activation in response to GWLs than the control warnings at a cluster-corrected threshold p <.001 in medial prefrontal cortex, amygdala, medial temporal lobe, and occipital cortex. There were no significant differences in response to warnings on branded versus plain cigarette packages. In this sample of young adult smokers, GWLs promoted neural activation in brain regions involved in cognitive and affective decision-making and memory formation and the effects of GWLs did not differ on branded or plain cigarette packaging. These findings complement other recent neuroimaging GWL studies conducted with older adult smokers and with adolescents by demonstrating similar patterns of neural activation in response to GWLs among young adult smokers.

  17. Neuron’s eye view: Inferring features of complex stimuli from neural responses

    PubMed Central

    Chen, Xin; Beck, Jeffrey M.

    2017-01-01

    Experiments that study neural encoding of stimuli at the level of individual neurons typically choose a small set of features present in the world—contrast and luminance for vision, pitch and intensity for sound—and assemble a stimulus set that systematically varies along these dimensions. Subsequent analysis of neural responses to these stimuli typically focuses on regression models, with experimenter-controlled features as predictors and spike counts or firing rates as responses. Unfortunately, this approach requires knowledge in advance about the relevant features coded by a given population of neurons. For domains as complex as social interaction or natural movement, however, the relevant feature space is poorly understood, and an arbitrary a priori choice of features may give rise to confirmation bias. Here, we present a Bayesian model for exploratory data analysis that is capable of automatically identifying the features present in unstructured stimuli based solely on neuronal responses. Our approach is unique within the class of latent state space models of neural activity in that it assumes that firing rates of neurons are sensitive to multiple discrete time-varying features tied to the stimulus, each of which has Markov (or semi-Markov) dynamics. That is, we are modeling neural activity as driven by multiple simultaneous stimulus features rather than intrinsic neural dynamics. We derive a fast variational Bayesian inference algorithm and show that it correctly recovers hidden features in synthetic data, as well as ground-truth stimulus features in a prototypical neural dataset. To demonstrate the utility of the algorithm, we also apply it to cluster neural responses and demonstrate successful recovery of features corresponding to monkeys and faces in the image set. PMID:28827790

  18. Metabotropic glutamate receptor 5 responses dictate differentiation of neural progenitors to NMDA-responsive cells in fragile X syndrome.

    PubMed

    Achuta, Venkat Swaroop; Grym, Heli; Putkonen, Noora; Louhivuori, Verna; Kärkkäinen, Virve; Koistinaho, Jari; Roybon, Laurent; Castrén, Maija L

    2017-04-01

    Disrupted metabotropic glutamate receptor 5 (mGluR5) signaling is implicated in many neuropsychiatric disorders, including autism spectrum disorder, found in fragile X syndrome (FXS). Here we report that intracellular calcium responses to the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) are augmented, and calcium-dependent mGluR5-mediated mechanisms alter the differentiation of neural progenitors in neurospheres derived from human induced pluripotent FXS stem cells and the brains of mouse model of FXS. Treatment with the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) prevents an abnormal clustering of DHPG-responsive cells that are responsive to activation of ionotropic receptors in mouse FXS neurospheres. MPEP also corrects morphological defects of differentiated cells and enhanced migration of neuron-like cells in mouse FXS neurospheres. Unlike in mouse neurospheres, MPEP increases the differentiation of DHPG-responsive radial glial cells as well as the subpopulation of cells responsive to both DHPG and activation of ionotropic receptors in human neurospheres. However, MPEP normalizes the FXS-specific increase in the differentiation of cells responsive only to N-methyl-d-aspartate (NMDA) present in human neurospheres. Exposure to MPEP prevents the accumulation of intermediate basal progenitors in embryonic FXS mouse brain suggesting that rescue effects of GluR5 antagonist are progenitor type-dependent and species-specific differences of basal progenitors may modify effects of MPEP on the cortical development. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017. © 2016 Wiley Periodicals, Inc.

  19. The Neural Correlates of Deficient Error Awareness in Attention-Deficit Hyperactivity Disorder (ADHD)

    ERIC Educational Resources Information Center

    O'Connell, Redmond G.; Bellgrove, Mark A.; Dockree, Paul M.; Lau, Adam; Hester, Robert; Garavan, Hugh; Fitzgerald, Michael; Foxe, John J.; Robertson, Ian H.

    2009-01-01

    The ability to detect and correct errors is critical to adaptive control of behaviour and represents a discrete neuropsychological function. A number of studies have highlighted that attention-deficit hyperactivity disorder (ADHD) is associated with abnormalities in behavioural and neural responsiveness to performance errors. One limitation of…

  20. Neural correlates of emotional responses to music: an EEG study.

    PubMed

    Daly, Ian; Malik, Asad; Hwang, Faustina; Roesch, Etienne; Weaver, James; Kirke, Alexis; Williams, Duncan; Miranda, Eduardo; Nasuto, Slawomir J

    2014-06-24

    This paper presents an EEG study into the neural correlates of music-induced emotions. We presented participants with a large dataset containing musical pieces in different styles, and asked them to report on their induced emotional responses. We found neural correlates of music-induced emotion in a number of frequencies over the pre-frontal cortex. Additionally, we found a set of patterns of functional connectivity, defined by inter-channel coherence measures, to be significantly different between groups of music-induced emotional responses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Do abnormal responses show utilitarian bias?

    PubMed

    Kahane, Guy; Shackel, Nicholas

    2008-03-20

    Neuroscience has recently turned to the study of utilitarian and non-utilitarian moral judgement. Koenigs et al. examine the responses of normal subjects and those with ventromedial-prefrontal-cortex (VMPC) damage to moral scenarios drawn from functional magnetic resonance imaging studies by Greene et al., and claim that patients with VMPC damage have an abnormally "utilitarian" pattern of moral judgement. It is crucial to the claims of Koenigs et al. that the scenarios of Greene et al. pose a conflict between utilitarian consequence and duty: however, many of them do not meet this condition. Because of this methodological problem, it is too early to claim that VMPC patients have a utilitarian bias.

  2. Rapid Postnatal Expansion of Neural Networks Occurs in an Environment of Altered Neurovascular and Neurometabolic Coupling.

    PubMed

    Kozberg, Mariel G; Ma, Ying; Shaik, Mohammed A; Kim, Sharon H; Hillman, Elizabeth M C

    2016-06-22

    In the adult brain, increases in neural activity lead to increases in local blood flow. However, many prior measurements of functional hemodynamics in the neonatal brain, including functional magnetic resonance imaging (fMRI) in human infants, have noted altered and even inverted hemodynamic responses to stimuli. Here, we demonstrate that localized neural activity in early postnatal mice does not evoke blood flow increases as in the adult brain, and elucidate the neural and metabolic correlates of these altered functional hemodynamics as a function of developmental age. Using wide-field GCaMP imaging, the development of neural responses to somatosensory stimulus is visualized over the entire bilaterally exposed cortex. Neural responses are observed to progress from tightly localized, unilateral maps to bilateral responses as interhemispheric connectivity becomes established. Simultaneous hemodynamic imaging confirms that spatiotemporally coupled functional hyperemia is not present during these early stages of postnatal brain development, and develops gradually as cortical connectivity is established. Exploring the consequences of this lack of functional hyperemia, measurements of oxidative metabolism via flavoprotein fluorescence suggest that neural activity depletes local oxygen to below baseline levels at early developmental stages. Analysis of hemoglobin oxygenation dynamics at the same age confirms oxygen depletion for both stimulus-evoked and resting-state neural activity. This state of unmet metabolic demand during neural network development poses new questions about the mechanisms of neurovascular development and its role in both normal and abnormal brain development. These results also provide important insights for the interpretation of fMRI studies of the developing brain. This work demonstrates that the postnatal development of neuronal connectivity is accompanied by development of the mechanisms that regulate local blood flow in response to neural

  3. Neural Mechanisms of Decision Making in Hoarding Disorder

    PubMed Central

    Tolin, David F.; Stevens, Michael C.; Villavicencio, Anna L.; Norberg, Melissa M.; Calhoun, Vince D.; Frost, Randy O.; Steketee, Gail; Rauch, Scott L.; Pearlson, Godfrey D.

    2012-01-01

    Context Hoarding disorder (HD), previously considered a subtype of obsessive-compulsive disorder (OCD), has been proposed as a unique diagnostic entity in DSM-5. Current models of HD emphasize problems of decision-making, attachment to possessions, and poor insight, whereas previous neuroimaging studies have suggested abnormalities in frontal brain regions. Objective To examine the neural mechanisms of impaired decision making in HD in patients with well-defined primary HD compared with patients with OCD and healthy control subjects (HCs). Design We compared neural activity among patients with HD, patients with OCD, and HCs during decisions to keep or discard personal possessions and control possessions from November 9, 2006, to August 13, 2010. Setting Private, not-for-profit hospital. Participants A total of 107 adults (43 with HD, 31 with OCD, and 33 HCs). Main Outcome Measures Neural activity as measured by functional magnetic resonance imaging in which actual real-time and binding decisions had to be made about whether to keep or discard possessions. Results Compared with participants with OCD and HC, participants with HD exhibited abnormal activity in the anterior cingulate cortex and insula that was stimulus dependent. Specifically, when deciding about items that did not belong to them, patients with HD showed relatively lower activity in these brain regions. However, when deciding about items that belonged to them, these regions showed excessive functional magnetic resonance imaging signals compared with the other 2 groups. These differences in neural function correlated significantly with hoarding severity and self-ratings of indecisiveness and “not just right” feelings among patients with HD and were unattributable to OCD or depressive symptoms. Conclusions Findings suggest a biphasic abnormality in anterior cingulate cortex and insula function in patients with HD related to problems in identifying the emotional significance of a stimulus, generating

  4. Neural mechanisms of decision making in hoarding disorder.

    PubMed

    Tolin, David F; Stevens, Michael C; Villavicencio, Anna L; Norberg, Melissa M; Calhoun, Vince D; Frost, Randy O; Steketee, Gail; Rauch, Scott L; Pearlson, Godfrey D

    2012-08-01

    Hoarding disorder (HD), previously considered a subtype of obsessive-compulsive disorder (OCD), has been proposed as a unique diagnostic entity in DSM-5. Current models of HD emphasize problems of decision-making, attachment to possessions, and poor insight, whereas previous neuroimaging studies have suggested abnormalities in frontal brain regions. To examine the neural mechanisms of impaired decision making in HD in patients with well-defined primary HD compared with patients with OCD and healthy control subjects (HCs). We compared neural activity among patients with HD, patients with OCD, and HCs during decisions to keep or discard personal possessions and control possessions from November 9, 2006, to August 13, 2010. Private, not-for-profit hospital. A total of 107 adults (43 with HD, 31 with OCD, and 33 HCs). Neural activity as measured by functional magnetic resonance imaging in which actual real-time and binding decisions had to be made about whether to keep or discard possessions. Compared with participants with OCD and HC, participants with HD exhibited abnormal activity in the anterior cingulate cortex and insula that was stimulus dependent. Specifically, when deciding about items that did not belong to them, patients with HD showed relatively lower activity in these brain regions. However, when deciding about items that belonged to them, these regions showed excessive functional magnetic resonance imaging signals compared with the other 2 groups. These differences in neural function correlated significantly with hoarding severity and self-ratings of indecisiveness and "not just right" feelings among patients with HD and were unattributable to OCD or depressive symptoms. Findings suggest a biphasic abnormality in anterior cingulate cortex and insula function in patients with HD related to problems in identifying the emotional significance of a stimulus, generating appropriate emotional response, or regulating affective state during decision making.

  5. Losartan corrects abnormal frequency response of renal vasculature in congestive heart failure.

    PubMed

    DiBona, Gerald F; Sawin, Linda L

    2003-11-01

    In congestive heart failure, renal blood flow is decreased and renal vascular resistance is increased in a setting of increased activity of both the sympathetic nervous and renin-angiotensin systems. The renal vasoconstrictor response to renal nerve stimulation is enhanced. This is associated with an abnormality in the low-pass filter function of the renal vasculature wherein higher frequencies (> or =0.01 Hz) within renal sympathetic nerve activity are not normally attenuated and are passed into the renal blood flow signal. This study tested the hypothesis that excess angiotensin II action mediates the abnormal frequency response characteristics of the renal vasculature in congestive heart failure. In anesthetized rats, the renal vasoconstrictor response to graded frequency renal nerve stimulation was significantly greater in congestive heart failure than in control rats. Losartan attenuated the renal vasoconstrictor response to a significantly greater degree in congestive heart failure than in control rats. In control rats, the frequency response of the renal vasculature was that of a first order (-20 dB/frequency decade) low-pass filter with a corner frequency (-3 dB, 30% attenuation) of 0.002 Hz and 97% attenuation (-30 dB) at > or =0.1 Hz. In congestive heart failure rats, attenuation did not exceed 45% (-5 dB) over the frequency range of 0.001-0.6 Hz. The frequency response of the renal vasculature was not affected by losartan treatment in control rats but was completely restored to normal by losartan treatment in congestive heart failure rats. The enhanced renal vasoconstrictor response to renal nerve stimulation and the associated abnormality in the frequency response characteristics of the renal vasculature seen in congestive heart failure are mediated by the action of angiotensin II on renal angiotensin II AT1 receptors.

  6. Visual Working Memory Enhances the Neural Response to Matching Visual Input.

    PubMed

    Gayet, Surya; Guggenmos, Matthias; Christophel, Thomas B; Haynes, John-Dylan; Paffen, Chris L E; Van der Stigchel, Stefan; Sterzer, Philipp

    2017-07-12

    Visual working memory (VWM) is used to maintain visual information available for subsequent goal-directed behavior. The content of VWM has been shown to affect the behavioral response to concurrent visual input, suggesting that visual representations originating from VWM and from sensory input draw upon a shared neural substrate (i.e., a sensory recruitment stance on VWM storage). Here, we hypothesized that visual information maintained in VWM would enhance the neural response to concurrent visual input that matches the content of VWM. To test this hypothesis, we measured fMRI BOLD responses to task-irrelevant stimuli acquired from 15 human participants (three males) performing a concurrent delayed match-to-sample task. In this task, observers were sequentially presented with two shape stimuli and a retro-cue indicating which of the two shapes should be memorized for subsequent recognition. During the retention interval, a task-irrelevant shape (the probe) was briefly presented in the peripheral visual field, which could either match or mismatch the shape category of the memorized stimulus. We show that this probe stimulus elicited a stronger BOLD response, and allowed for increased shape-classification performance, when it matched rather than mismatched the concurrently memorized content, despite identical visual stimulation. Our results demonstrate that VWM enhances the neural response to concurrent visual input in a content-specific way. This finding is consistent with the view that neural populations involved in sensory processing are recruited for VWM storage, and it provides a common explanation for a plethora of behavioral studies in which VWM-matching visual input elicits a stronger behavioral and perceptual response. SIGNIFICANCE STATEMENT Humans heavily rely on visual information to interact with their environment and frequently must memorize such information for later use. Visual working memory allows for maintaining such visual information in the mind

  7. Neural Responses to Central and Peripheral Objects in the Lateral Occipital Cortex

    PubMed Central

    Wang, Bin; Guo, Jiayue; Yan, Tianyi; Ohno, Seiichiro; Kanazawa, Susumu; Huang, Qiang; Wu, Jinglong

    2016-01-01

    Human object recognition and classification depend on the retinal location where the object is presented and decrease as eccentricity increases. The lateral occipital complex (LOC) is thought to be preferentially involved in the processing of objects, and its neural responses exhibit category biases to objects presented in the central visual field. However, the nature of LOC neural responses to central and peripheral objects remains largely unclear. In the present study, we used functional magnetic resonance imaging (fMRI) and a wide-view presentation system to investigate neural responses to four categories of objects (faces, houses, animals, and cars) in the primary visual cortex (V1) and the lateral visual cortex, including the LOC and the retinotopic areas LO-1 and LO-2. In these regions, the neural responses to objects decreased as the distance between the location of presentation and center fixation increased, which is consistent with the diminished perceptual ability that was found for peripherally presented images. The LOC and LO-2 exhibited significantly positive neural responses to all eccentricities (0–55°), but LO-1 exhibited significantly positive responses only to central eccentricities (0–22°). By measuring the ratio relative to V1 (RRV1), we further demonstrated that eccentricity, category and the interaction between them significantly affected neural processing in these regions. LOC, LO-1, and LO-2 exhibited larger RRV1s when stimuli were presented at an eccentricity of 0° compared to when they were presented at the greater eccentricities. In LOC and LO-2, the RRV1s for images of faces, animals and cars showed an increasing trend when the images were presented at eccentricities of 11 to 33°. However, the RRV1s for houses showed a decreasing trend in LO-1 and no difference in the LOC and LO-2. We hypothesize, that when houses and the images in the other categories were presented in the peripheral visual field, they were processed via

  8. Abnormalities of hybrid grouper (Epinephelus fuscoguttatus x Epinephelus lanceolatus) in Situbondo

    NASA Astrophysics Data System (ADS)

    Triastuti, J.; Pursetyo, K. T.; Monica, A.; Lutfiyah, L.; Budi, D. S.

    2018-04-01

    Grouper is one of consumption fish which is demanded excessively by local consumers and foreign consumers. Hybridization of grouper has been performed considerably that produce the good genetic quality of hybrid variants. One of grouper fish which has good genetic in its growth is kertang grouper fish. Nowadays many hatcheries performing hybridization between kertang grouper fish and tiger grouper fish, however observation of the hybrid abnormality has not been performed yet. Abnormality is able to increase since genetic causes, so that observation of abnormality occurrence in cantang hybrid grouper fish in Situbondo, JawaTimur, Indonesia in May – July in 3 times grading of juvenile stadia was performed. Results showed abnormalities were observed on mouth and operculum, branched of neural arch, fusion of neural arch, fusion of posterior truncus vertebrae, fusion of caudal vertebrae, fusion of anterior truncus vertebrae.

  9. Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study.

    PubMed

    Cadenas-Benitez, N M; Yanes-Sosa, F; Gonzalez-Meneses, A; Cerrillos, L; Acosta, D; Praena-Fernandez, J M; Neth, O; Gomez de Terreros, I; Ybot-González, P

    2014-03-26

    Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.

  10. Spreading Photoparoxysmal EEG Response is Associated with an Abnormal Cortical Excitability Pattern

    ERIC Educational Resources Information Center

    Siniatchkin, Michael; Groppa, Sergey; Jerosch, Bettina; Muhle, Hiltrud; Kurth, Christoph; Shepherd, Alex J.; Siebner, Hartwig; Stephani, Ulrich

    2007-01-01

    Photosensitivity or photoparoxysmal response (PPR) is a highly heritable electroencephalographic trait characterized by an abnormal cortical response to intermittent photic stimulation (IPS). In PPR-positive individuals, IPS induces spikes, spike-waves or intermittent slow waves. The PPR may be restricted to posterior visual areas (i.e. local PPR…

  11. Abnormal late visual responses and alpha oscillations in neurofibromatosis type 1: a link to visual and attention deficits

    PubMed Central

    2014-01-01

    Background Neurofibromatosis type 1 (NF1) affects several areas of cognitive function including visual processing and attention. We investigated the neural mechanisms underlying the visual deficits of children and adolescents with NF1 by studying visual evoked potentials (VEPs) and brain oscillations during visual stimulation and rest periods. Methods Electroencephalogram/event-related potential (EEG/ERP) responses were measured during visual processing (NF1 n = 17; controls n = 19) and idle periods with eyes closed and eyes open (NF1 n = 12; controls n = 14). Visual stimulation was chosen to bias activation of the three detection mechanisms: achromatic, red-green and blue-yellow. Results We found significant differences between the groups for late chromatic VEPs and a specific enhancement in the amplitude of the parieto-occipital alpha amplitude both during visual stimulation and idle periods. Alpha modulation and the negative influence of alpha oscillations in visual performance were found in both groups. Conclusions Our findings suggest abnormal later stages of visual processing and enhanced amplitude of alpha oscillations supporting the existence of deficits in basic sensory processing in NF1. Given the link between alpha oscillations, visual perception and attention, these results indicate a neural mechanism that might underlie the visual sensitivity deficits and increased lapses of attention observed in individuals with NF1. PMID:24559228

  12. Neural correlates of own- and other-race face perception: spatial and temporal response differences.

    PubMed

    Natu, Vaidehi; Raboy, David; O'Toole, Alice J

    2011-02-01

    Humans show an "other-race effect" for face recognition, with more accurate recognition of own- versus other-race faces. We compared the neural representations of own- and other-race faces using functional magnetic resonance imaging (fMRI) data in combination with a multi-voxel pattern classifier. Neural activity was recorded while Asians and Caucasians viewed Asian and Caucasian faces. A pattern classifier, applied to voxels across a broad range of ventral temporal areas, discriminated the brain activity maps elicited in response to Asian versus Caucasian faces in the brains of both Asians and Caucasians. Classification was most accurate in the first few time points of the block and required the use of own-race faces in the localizer scan to select voxels for classifier input. Next, we examined differences in the time-course of neural responses to own- and other-race faces and found evidence for a temporal "other-race effect." Own-race faces elicited a larger neural response initially that attenuated rapidly. The response to other-race faces was weaker at first, but increased over time, ultimately surpassing the magnitude of the own-race response in the fusiform "face" area (FFA). A similar temporal response pattern held across a broad range of ventral temporal areas. The pattern-classification results indicate the early availability of categorical information about own- versus other-race face status in the spatial pattern of neural activity. The slower, more sustained, brain response to other-race faces may indicate the need to recruit additional neural resources to process other-race faces for identification. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Temporal binding of neural responses for focused attention in biosonar

    PubMed Central

    Simmons, James A.

    2014-01-01

    Big brown bats emit biosonar sounds and perceive their surroundings from the delays of echoes received by the ears. Broadcasts are frequency modulated (FM) and contain two prominent harmonics sweeping from 50 to 25 kHz (FM1) and from 100 to 50 kHz (FM2). Individual frequencies in each broadcast and each echo evoke single-spike auditory responses. Echo delay is encoded by the time elapsed between volleys of responses to broadcasts and volleys of responses to echoes. If echoes have the same spectrum as broadcasts, the volley of neural responses to FM1 and FM2 is internally synchronized for each sound, which leads to sharply focused delay images. Because of amplitude–latency trading, disruption of response synchrony within the volleys occurs if the echoes are lowpass filtered, leading to blurred, defocused delay images. This effect is consistent with the temporal binding hypothesis for perceptual image formation. Bats perform inexplicably well in cluttered surroundings where echoes from off-side objects ought to cause masking. Off-side echoes are lowpass filtered because of the shape of the broadcast beam, and they evoke desynchronized auditory responses. The resulting defocused images of clutter do not mask perception of focused images for targets. Neural response synchronization may select a target to be the focus of attention, while desynchronization may impose inattention on the surroundings by defocusing perception of clutter. The formation of focused biosonar images from synchronized neural responses, and the defocusing that occurs with disruption of synchrony, quantitatively demonstrates how temporal binding may control attention and bring a perceptual object into existence. PMID:25122915

  14. Temporal binding of neural responses for focused attention in biosonar.

    PubMed

    Simmons, James A

    2014-08-15

    Big brown bats emit biosonar sounds and perceive their surroundings from the delays of echoes received by the ears. Broadcasts are frequency modulated (FM) and contain two prominent harmonics sweeping from 50 to 25 kHz (FM1) and from 100 to 50 kHz (FM2). Individual frequencies in each broadcast and each echo evoke single-spike auditory responses. Echo delay is encoded by the time elapsed between volleys of responses to broadcasts and volleys of responses to echoes. If echoes have the same spectrum as broadcasts, the volley of neural responses to FM1 and FM2 is internally synchronized for each sound, which leads to sharply focused delay images. Because of amplitude-latency trading, disruption of response synchrony within the volleys occurs if the echoes are lowpass filtered, leading to blurred, defocused delay images. This effect is consistent with the temporal binding hypothesis for perceptual image formation. Bats perform inexplicably well in cluttered surroundings where echoes from off-side objects ought to cause masking. Off-side echoes are lowpass filtered because of the shape of the broadcast beam, and they evoke desynchronized auditory responses. The resulting defocused images of clutter do not mask perception of focused images for targets. Neural response synchronization may select a target to be the focus of attention, while desynchronization may impose inattention on the surroundings by defocusing perception of clutter. The formation of focused biosonar images from synchronized neural responses, and the defocusing that occurs with disruption of synchrony, quantitatively demonstrates how temporal binding may control attention and bring a perceptual object into existence. © 2014. Published by The Company of Biologists Ltd.

  15. Linking normative models of natural tasks to descriptive models of neural response.

    PubMed

    Jaini, Priyank; Burge, Johannes

    2017-10-01

    Understanding how nervous systems exploit task-relevant properties of sensory stimuli to perform natural tasks is fundamental to the study of perceptual systems. However, there are few formal methods for determining which stimulus properties are most useful for a given natural task. As a consequence, it is difficult to develop principled models for how to compute task-relevant latent variables from natural signals, and it is difficult to evaluate descriptive models fit to neural response. Accuracy maximization analysis (AMA) is a recently developed Bayesian method for finding the optimal task-specific filters (receptive fields). Here, we introduce AMA-Gauss, a new faster form of AMA that incorporates the assumption that the class-conditional filter responses are Gaussian distributed. Then, we use AMA-Gauss to show that its assumptions are justified for two fundamental visual tasks: retinal speed estimation and binocular disparity estimation. Next, we show that AMA-Gauss has striking formal similarities to popular quadratic models of neural response: the energy model and the generalized quadratic model (GQM). Together, these developments deepen our understanding of why the energy model of neural response have proven useful, improve our ability to evaluate results from subunit model fits to neural data, and should help accelerate psychophysics and neuroscience research with natural stimuli.

  16. Sex differences in associations between cannabis craving and neural responses to cannabis cues: Implications for treatment.

    PubMed

    Wetherill, Reagan R; Jagannathan, Kanchana; Hager, Nathan; Childress, Anna Rose; Franklin, Teresa R

    2015-08-01

    Preclinical and clinical research indicates that there are sex differences in how men and women initiate, progress, respond to, and withdraw from cannabis use; however, neurophysiological differences, such as neural responses to cannabis cues, are not well understood. Using functional MRI and an event-related blood oxygen level-dependent backward-masking task, we compared neural responses to backward-masked cannabis cues to neutral cues in treatment-seeking, cannabis-dependent adults (N = 44; 27 males) and examined whether sex differences exist. In addition, functional MRI findings were correlated with cannabis craving. Backward-masked cannabis cues elicited greater neural responses than neutral cues in reward-related brain regions, including the striatum, hippocampus/amygdala, insula, anterior cingulate cortex, and lateral orbitofrontal cortex, p < .01, k > 121 voxels. Although no significant sex differences in neural responses to cannabis cues emerged, women showed a positive correlation between neural responses to cannabis cues in the bilateral insula and cannabis craving and an inverse correlation between neural responses to cannabis cues in the left lateral orbitofrontal cortex and cannabis craving. Men, however, showed a positive correlation between neural responses to cannabis cues in the striatum and cannabis craving. Given that cues and craving are important triggers and the focus on many behavioral treatment approaches, these findings suggest that treatment-seeking, cannabis-dependent men and women may benefit from sex-specific and tailored cannabis use disorder treatments. (c) 2015 APA, all rights reserved).

  17. The Neural Crest in Cardiac Congenital Anomalies

    PubMed Central

    Keyte, Anna; Hutson, Mary Redmond

    2012-01-01

    This review discusses the function of neural crest as they relate to cardiovascular defects. The cardiac neural crest cells are a subpopulation of cranial neural crest discovered nearly 30 years ago by ablation of premigratory neural crest. The cardiac neural crest cells are necessary for normal cardiovascular development. We begin with a description of the crest cells in normal development, including their function in remodeling the pharyngeal arch arteries, outflow tract septation, valvulogenesis, and development of the cardiac conduction system. The cells are also responsible for modulating signaling in the caudal pharynx, including the second heart field. Many of the molecular pathways that are known to influence specification, migration, patterning and final targeting of the cardiac neural crest cells are reviewed. The cardiac neural crest cells play a critical role in the pathogenesis of various human cardiocraniofacial syndromes such as DiGeorge, Velocardiofacial, CHARGE, Fetal Alcohol, Alagille, LEOPARD, and Noonan syndromes, as well as Retinoic Acid Embryopathy. The loss of neural crest cells or their dysfunction may not always directly cause abnormal cardiovascular development, but are involved secondarily because crest cells represent a major component in the complex tissue interactions in the head, pharynx and outflow tract. Thus many of the human syndromes linking defects in the heart, face and brain can be better understood when considered within the context of a single cardiocraniofacial developmental module with the neural crest being a key cell type that interconnects the regions. PMID:22595346

  18. Audiological characteristics of infants with abnormal transient evoked otoacoustic emission and normal auditory brainstem response.

    PubMed

    Huang, Lihui; Han, Demin; Guo, Ying; Liu, Sha; Cui, Xiaoyan; Mo, Lingyan; Qi, Beier; Cai, Zhenghua; Liu, Hui; En, Hui; Guo, Liansheng

    2008-10-01

    Audiological characteristics were investigated in 81 ears of 53 infants with abnormal transient evoked otoacoustic emission (TEOAE) and normal auditory brainstem response (ABR). The relationship between ABR and other hearing testing methods, including 40Hz auditory event-related potential (40Hz-AERP), auditory steady state response (ASSR), distortion product otoacoustic emission (DPOAE), tympanometry, and acoustic reflex, was analyzed. Of the 81 ears, 18 ears (22.2%) were normal, while 63 ears (77.8%) were abnormal according to the tests. Testing of the 40 Hz AERP (36 ears) and ASSR (45 ears) revealed that 14 ears (38.9%) and 27 ears (60.0%) were abnormal, respectively. Testing of DPOAE in 68 ears revealed that 50 ears (73.5%) were abnormal. Testing of tympanometry in 50 ears and acoustic reflex in 47 ears revealed that 9 ears (18%) and 27 ears (57.4%) were abnormal, respectively. The present data suggests that the hearing of infants cannot be sufficiently evaluated with ABR only and that it must be evaluated with integrative audiological testing methods.

  19. Mechanisms determining cholinergic neural responses in airways of young and mature rabbits.

    PubMed

    Larsen, Gary L; Loader, Joan; Nguyen, Dee Dee; Fratelli, Cori; Dakhama, Azzeddine; Colasurdo, Giuseppe N

    2004-08-01

    Neural pathways help control airway caliber and responsiveness. Yet little is known of how neural control changes as a function of development. In rabbits, we found electrical field stimulation (EFS) of airway nerves led to more marked contractile responses in 2- vs. 13-week-old animals. This enhanced response to EFS may be due to prejunctional, junctional, and/or postjunctional neural mechanisms. We assessed these mechanisms in airways of 2- and 13-week-old rabbits. The contractile responses to methacholine did not differ in the groups, suggesting postjunctional neural events are not primarily responsible for differing responses to EFS. To address junctional events, acetylcholinesterase (AChE) was measured (spectrophotometry). AChE was elevated in 2-week-olds. However, this should lead to less and not greater responses. Prejunctionally, EFS-induced acetylcholine (ACh) release was assessed by HPLC. Airways of 2-week-old rabbits released significantly more ACh than airways from mature rabbits. Choline acetyltransferase, a marker of cholinergic nerves, was not different between groups, suggesting that more ACh release in young rabbits was not due to increased nerve density. ACh release in the presence of polyarginine increased significantly in both groups, supporting the presence of functional muscarinic autoreceptors (M2) at both ages. Because substance P (SP) increases release of ACh, SP was measured by ELISA. This neuropeptide was significantly elevated in airways of younger rabbits. Nerve growth factor (NGF) increased SP and was also significantly increased in airways from younger rabbits. This work suggests that increases in EFS-induced responsiveness in young rabbits are likely due to prejunctional events with enhanced release of ACh. Increases in NGF and SP early in life may contribute to this increased responsiveness. Copyright 2004 Wiley-Liss, Inc.

  20. Neural attention and evaluative responses to gay and lesbian couples.

    PubMed

    Dickter, Cheryl L; Forestell, Catherine A; Mulder, Blakely E

    2015-01-01

    The goal of the current study was to examine whether differential neural attentional capture and evaluative responses for out-group homosexual relative to in-group heterosexual targets occur during social categorization. To this end, 36 heterosexual participants were presented with pictures of heterosexual and homosexual couples in a picture-viewing task that was designed to assess implicit levels of discomfort toward homosexuality and explicit evaluations of pleasantness toward the images. Neural activity in the form of electroencephalogram was recorded during the presentation of the pictures, and event-related potentials resulting from these stimuli were examined. Participants also completed questionnaires that assessed the degree to which they socialized with gays and lesbians. Results demonstrated that relative to straight couples, larger P2 amplitude was observed in response to gay but not to lesbian couples. However, both gay and lesbian couples yielded a larger late positive potential than straight couples. Moreover, the degree to which participants differentially directed early neural attention to out-group lesbian versus in-group straight couples was related to their familiarity with homosexual individuals. This work, which provides an initial understanding of the neural underpinnings of attention toward homosexual couples, suggests that differences in the processing of sexual orientation can occur as early as 200 ms and may be moderated by familiarity.

  1. Primary prevention of neural-tube defects and some other congenital abnormalities by folic acid and multivitamins: history, missed opportunity and tasks

    PubMed Central

    Bártfai, Zoltán; Bánhidy, Ferenc

    2011-01-01

    The history of intervention trials of periconception folic acid with multivitamin and folic acid supplementation in women has shown a recent breakthrough in the primary prevention of structural birth defects, namely neural-tube defects and some other congenital abnormalities. Recently, some studies have demonstrated the efficacy of this new method in reducing congenital abnormalities with specific origin; for example, in the offspring of diabetic and epileptic mothers, and in pregnancy with high fever. The benefits and drawbacks of four possible uses of periconception folate/folic acid and multivitamin supplementation are discussed: we believe there has been a missed opportunity to implement this preventive approach in medical practice. The four methods are as follows: (i) dietary intake of folate and other vitamins, (ii) periconception folic acid/multivitamin supplementation, (iii) food fortification with folic acid, and (iv) the combination of oral contraceptives with 6S-5-methytetrahydrofolate (‘folate’). PMID:25083211

  2. Neural responses of rat cortical layers due to infrared neural modulation and photoablation of thalamocortical brain slices

    NASA Astrophysics Data System (ADS)

    Jenkins, J. Logan; Kao, Chris C.; Cayce, Jonathan M.; Mahadevan-Jansen, Anita; Jansen, E. Duco

    2017-02-01

    Infrared neural modulation (INM) is a label-free method for eliciting neural activity with high spatial selectivity in mammalian models. While there has been an emphasis on INM research towards applications in the peripheral nervous system and the central nervous system (CNS), the biophysical mechanisms by which INM occurs remains largely unresolved. In the rat CNS, INM has been shown to elicit and inhibit neural activity, evoke calcium signals that are dependent on glutamate transients and astrocytes, and modulate inhibitory GABA currents. So far, in vivo experiments have been restricted to layers I and II of the rat cortex which consists mainly of astrocytes, inhibitory neurons, and dendrites from deeper excitatory neurons owing to strong absorption of light in these layers. Deeper cortical layers (III-VI) have vastly different cell type composition, consisting predominantly of excitatory neurons which can be targeted for therapies such as deep brain stimulation. The neural responses to infrared light of deeper cortical cells have not been well defined. Acute thalamocortical brain slices will allow us to analyze the effects of INS on various components of the cortex, including different cortical layers and cell populations. In this study, we present the use of photoablation with an erbium:YAG laser to reduce the thickness of the dead cell zone near the cutting surface of brain slices. This technique will allow for more optical energy to reach living cells, which should contribute the successful transduction of pulsed infrared light to neural activity. In the future, INM-induced neural responses will lead to a finer characterization of the parameter space for the neuromodulation of different cortical cell types and may contribute to understanding the cell populations that are important for allowing optical stimulation of neurons in the CNS.

  3. Are automatic postural responses in patients with Parkinson's disease abnormal due to their stooped posture?

    PubMed

    Bloem, B R; Beckley, D J; van Dijk, J G

    1999-02-01

    Abnormal automatic postural responses are thought to contribute to balance impairment in Parkinson's disease. However, because postural responses are modifiable by stance, we have speculated that some postural abnormalities in patients with Parkinson's disease are secondary to their stooped stance. We have studied this assumption by assessing automatic postural responses in 30 healthy subjects who were instructed either to stand upright or to assume a typical parkinsonian posture. During both conditions, subjects received 20 serial 4 degrees 'toe-up' rotational perturbations from a supporting forceplate. We recorded short-latency (SL) and medium-latency (ML) responses from stretched gastrocnemius muscles and long-latency (LL) responses from shortened tibialis anterior muscles. We also assessed changes in the center of foot pressure (CFP) and the center of gravity (COG). The results were qualitatively compared to a previously described group of patients with Parkinson's disease who, under these circumstances, typically have large ML responses, small LL responses and insufficient voluntary postural corrections, accompanied by a slow rate of backward CFP displacement and an increased posterior COG displacement. The stooped posture resulted in unloading of medial gastrocnemius muscles and loading of tibialis anterior muscles. Onset latencies of stretch responses in gastrocnemius muscles were delayed in stooped subjects, but the onset of LL responses was markedly reduced. Amplitudes of both ML and LL responses were reduced in stooped subjects. Prestimulus COG and, to a lesser extent, CFP were shifted forwards in stooped subjects. Posterior COG displacement and the rate of backward CFP displacement were diminished in stooped subjects. Voluntary postural corrections were unchanged while standing stooped. These results indicate that some postural abnormalities of patients with Parkinson's disease (most notably the reduced LL responses) can be reproduced in healthy subjects

  4. Socioeconomic disadvantage, neural responses to infant emotions, and emotional availability among first-time new mothers.

    PubMed

    Kim, Pilyoung; Capistrano, Christian G; Erhart, Andrew; Gray-Schiff, Rachel; Xu, Nanxi

    2017-05-15

    During the early postpartum period, mothers exhibit increased amygdala responses to positive infant expressions, which are important for positive mother-infant relationships. Socioeconomic disadvantage is associated with altered amygdala response to emotional stimuli as well as more negative mother-infant relationships. However, little is known about the role of socioeconomic disadvantage in neural responses specifically to infants. Thus, we examined whether socioeconomic disadvantage (indexed by lower income-to-needs ratio) is associated with neural responses to infant emotions and parenting behaviors among new mothers. Using fMRI, neural responses to infants' emotional expressions (positive, negative, and neutral faces) were assessed among 39 low- and middle-income first-time mothers during 0-6 postpartum months. Lower income-to-needs ratio was associated with dampened amygdala responses to positive infant faces, but increased amygdala responses to negative infant faces. An indirect effect of socioeconomic disadvantage on emotional availability via amygdala activation suggests that socioeconomic disadvantage is associated with heightened neural sensitivity to infants' negative emotions, which is further associated with mothers' intrusiveness observed during interactions with their own infant. The findings suggest that low-income mothers may be more vulnerable to altered neural processing of infants' emotional expressions which may further influence mothers' emotional availability during interactions with their own infants. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A neural network model of normal and abnormal auditory information processing.

    PubMed

    Du, X; Jansen, B H

    2011-08-01

    The ability of the brain to attenuate the response to irrelevant sensory stimulation is referred to as sensory gating. A gating deficiency has been reported in schizophrenia. To study the neural mechanisms underlying sensory gating, a neuroanatomically inspired model of auditory information processing has been developed. The mathematical model consists of lumped parameter modules representing the thalamus (TH), the thalamic reticular nucleus (TRN), auditory cortex (AC), and prefrontal cortex (PC). It was found that the membrane potential of the pyramidal cells in the PC module replicated auditory evoked potentials, recorded from the scalp of healthy individuals, in response to pure tones. Also, the model produced substantial attenuation of the response to the second of a pair of identical stimuli, just as seen in actual human experiments. We also tested the viewpoint that schizophrenia is associated with a deficit in prefrontal dopamine (DA) activity, which would lower the excitatory and inhibitory feedback gains in the AC and PC modules. Lowering these gains by less than 10% resulted in model behavior resembling the brain activity seen in schizophrenia patients, and replicated the reported gating deficits. The model suggests that the TRN plays a critical role in sensory gating, with the smaller response to a second tone arising from a reduction in inhibition of TH by the TRN. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Application of Neural Networks to Wind tunnel Data Response Surface Methods

    NASA Technical Reports Server (NTRS)

    Lo, Ching F.; Zhao, J. L.; DeLoach, Richard

    2000-01-01

    The integration of nonlinear neural network methods with conventional linear regression techniques is demonstrated for representative wind tunnel force balance data modeling. This work was motivated by a desire to formulate precision intervals for response surfaces produced by neural networks. Applications are demonstrated for representative wind tunnel data acquired at NASA Langley Research Center and the Arnold Engineering Development Center in Tullahoma, TN.

  7. Analyzing multicomponent receptive fields from neural responses to natural stimuli

    PubMed Central

    Rowekamp, Ryan; Sharpee, Tatyana O

    2011-01-01

    The challenge of building increasingly better models of neural responses to natural stimuli is to accurately estimate the multiple stimulus features that may jointly affect the neural spike probability. The selectivity for combinations of features is thought to be crucial for achieving classical properties of neural responses such as contrast invariance. The joint search for these multiple stimulus features is difficult because estimating spike probability as a multidimensional function of stimulus projections onto candidate relevant dimensions is subject to the curse of dimensionality. An attractive alternative is to search for relevant dimensions sequentially, as in projection pursuit regression. Here we demonstrate using analytic arguments and simulations of model cells that different types of sequential search strategies exhibit systematic biases when used with natural stimuli. Simulations show that joint optimization is feasible for up to three dimensions with current algorithms. When applied to the responses of V1 neurons to natural scenes, models based on three jointly optimized dimensions had better predictive power in a majority of cases compared to dimensions optimized sequentially, with different sequential methods yielding comparable results. Thus, although the curse of dimensionality remains, at least several relevant dimensions can be estimated by joint information maximization. PMID:21780916

  8. Neural Network and Response Surface Methodology for Rocket Engine Component Optimization

    NASA Technical Reports Server (NTRS)

    Vaidyanathan, Rajkumar; Papita, Nilay; Shyy, Wei; Tucker, P. Kevin; Griffin, Lisa W.; Haftka, Raphael; Fitz-Coy, Norman; McConnaughey, Helen (Technical Monitor)

    2000-01-01

    The goal of this work is to compare the performance of response surface methodology (RSM) and two types of neural networks (NN) to aid preliminary design of two rocket engine components. A data set of 45 training points and 20 test points obtained from a semi-empirical model based on three design variables is used for a shear coaxial injector element. Data for supersonic turbine design is based on six design variables, 76 training, data and 18 test data obtained from simplified aerodynamic analysis. Several RS and NN are first constructed using the training data. The test data are then employed to select the best RS or NN. Quadratic and cubic response surfaces. radial basis neural network (RBNN) and back-propagation neural network (BPNN) are compared. Two-layered RBNN are generated using two different training algorithms, namely solverbe and solverb. A two layered BPNN is generated with Tan-Sigmoid transfer function. Various issues related to the training of the neural networks are addressed including number of neurons, error goals, spread constants and the accuracy of different models in representing the design space. A search for the optimum design is carried out using a standard gradient-based optimization algorithm over the response surfaces represented by the polynomials and trained neural networks. Usually a cubic polynominal performs better than the quadratic polynomial but exceptions have been noticed. Among the NN choices, the RBNN designed using solverb yields more consistent performance for both engine components considered. The training of RBNN is easier as it requires linear regression. This coupled with the consistency in performance promise the possibility of it being used as an optimization strategy for engineering design problems.

  9. Neural Markers of Responsiveness to the Environment in Human Sleep.

    PubMed

    Andrillon, Thomas; Poulsen, Andreas Trier; Hansen, Lars Kai; Léger, Damien; Kouider, Sid

    2016-06-15

    Sleep is characterized by a loss of behavioral responsiveness. However, recent research has shown that the sleeping brain is not completely disconnected from its environment. How neural activity constrains the ability to process sensory information while asleep is yet unclear. Here, we instructed human volunteers to classify words with lateralized hand responses while falling asleep. Using an electroencephalographic (EEG) marker of motor preparation, we show how responsiveness is modulated across sleep. These modulations are tracked using classic event-related potential analyses complemented by Lempel-Ziv complexity (LZc), a measure shown to track arousal in sleep and anesthesia. Neural activity related to the semantic content of stimuli was conserved in light non-rapid eye movement (NREM) sleep. However, these processes were suppressed in deep NREM sleep and, importantly, also in REM sleep, despite the recovery of wake-like neural activity in the latter. In NREM sleep, sensory activations were counterbalanced by evoked down states, which, when present, blocked further processing of external information. In addition, responsiveness markers correlated positively with baseline complexity, which could be related to modulation in sleep depth. In REM sleep, however, this relationship was reversed. We therefore propose that, in REM sleep, endogenously generated processes compete with the processing of external input. Sleep can thus be seen as a self-regulated process in which external information can be processed in lighter stages but suppressed in deeper stages. Last, our results suggest drastically different gating mechanisms in NREM and REM sleep. Previous research has tempered the notion that sleepers are isolated from their environment. Here, we pushed this idea forward and examined, across all sleep stages, the brain's ability to flexibly process sensory information, up to the decision level. We extracted an EEG marker of motor preparation to determine the

  10. A novel method for extraction of neural response from single channel cochlear implant auditory evoked potentials.

    PubMed

    Sinkiewicz, Daniel; Friesen, Lendra; Ghoraani, Behnaz

    2017-02-01

    Cortical auditory evoked potentials (CAEP) are used to evaluate cochlear implant (CI) patient auditory pathways, but the CI device produces an electrical artifact, which obscures the relevant information in the neural response. Currently there are multiple methods, which attempt to recover the neural response from the contaminated CAEP, but there is no gold standard, which can quantitatively confirm the effectiveness of these methods. To address this crucial shortcoming, we develop a wavelet-based method to quantify the amount of artifact energy in the neural response. In addition, a novel technique for extracting the neural response from single channel CAEPs is proposed. The new method uses matching pursuit (MP) based feature extraction to represent the contaminated CAEP in a feature space, and support vector machines (SVM) to classify the components as normal hearing (NH) or artifact. The NH components are combined to recover the neural response without artifact energy, as verified using the evaluation tool. Although it needs some further evaluation, this approach is a promising method of electrical artifact removal from CAEPs. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

  11. Relation of obesity to neural activation in response to food commercials

    PubMed Central

    Yokum, Sonja; Stice, Eric; Harris, Jennifer L.; Brownell, Kelly D.

    2014-01-01

    Adolescents view thousands of food commercials annually, but the neural response to food advertising and its association with obesity is largely unknown. This study is the first to examine how neural response to food commercials differs from other stimuli (e.g. non-food commercials and television show) and to explore how this response may differ by weight status. The blood oxygen level-dependent functional magnetic resonance imaging activation was measured in 30 adolescents ranging from lean to obese in response to food and non-food commercials imbedded in a television show. Adolescents exhibited greater activation in regions implicated in visual processing (e.g. occipital gyrus), attention (e.g. parietal lobes), cognition (e.g. temporal gyrus and posterior cerebellar lobe), movement (e.g. anterior cerebellar cortex), somatosensory response (e.g. postcentral gyrus) and reward [e.g. orbitofrontal cortex and anterior cingulate cortex (ACC)] during food commercials. Obese participants exhibited less activation during food relative to non-food commercials in neural regions implicated in visual processing (e.g. cuneus), attention (e.g. posterior cerebellar lobe), reward (e.g. ventromedial prefrontal cortex and ACC) and salience detection (e.g. precuneus). Obese participants did exhibit greater activation in a region implicated in semantic control (e.g. medial temporal gyrus). These findings may inform current policy debates regarding the impact of food advertising to minors. PMID:23576811

  12. Neural responses to exclusion predict susceptibility to social influence.

    PubMed

    Falk, Emily B; Cascio, Christopher N; O'Donnell, Matthew Brook; Carp, Joshua; Tinney, Francis J; Bingham, C Raymond; Shope, Jean T; Ouimet, Marie Claude; Pradhan, Anuj K; Simons-Morton, Bruce G

    2014-05-01

    Social influence is prominent across the lifespan, but sensitivity to influence is especially high during adolescence and is often associated with increased risk taking. Such risk taking can have dire consequences. For example, in American adolescents, traffic-related crashes are leading causes of nonfatal injury and death. Neural measures may be especially useful in understanding the basic mechanisms of adolescents' vulnerability to peer influence. We examined neural responses to social exclusion as potential predictors of risk taking in the presence of peers in recently licensed adolescent drivers. Risk taking was assessed in a driving simulator session occurring approximately 1 week after the neuroimaging session. Increased activity in neural systems associated with the distress of social exclusion and mentalizing during an exclusion episode predicted increased risk taking in the presence of a peer (controlling for solo risk behavior) during a driving simulator session outside the neuroimaging laboratory 1 week later. These neural measures predicted risky driving behavior above and beyond self-reports of susceptibility to peer pressure and distress during exclusion. These results address the neural bases of social influence and risk taking; contribute to our understanding of social and emotional function in the adolescent brain; and link neural activity in specific, hypothesized, regions to risk-relevant outcomes beyond the neuroimaging laboratory. Results of this investigation are discussed in terms of the mechanisms underlying risk taking in adolescents and the public health implications for adolescent driving. Copyright © 2014 Society for Adolescent Health and Medicine. All rights reserved.

  13. Neural responses to exclusion predict susceptibility to social influence

    PubMed Central

    Falk, Emily B.; Cascio, Christopher N.; O’Donnell, Matthew Brook; Carp, Joshua; Tinney, Francis J.; Bingham, C. Raymond; Shope, Jean T.; Ouimet, Marie Claude; Pradhan, Anuj K.; Simons-Morton, Bruce G.

    2014-01-01

    Purpose Social influence is prominent across the lifespan, but sensitivity to influence is especially high during adolescence, and is often associated with increased risk taking. Such risk taking can have dire consequences. For example, in American teens, traffic-related crashes are leading causes of non-fatal injury and death. Neural measures may be especially useful in understanding the basic mechanisms of adolescents’ vulnerability to peer influence. Methods We examined neural responses to social exclusion as potential predictors of risk taking in the presence of peers in recently-licensed adolescent drivers. Risk taking was assessed in a driving simulator session occurring approximately one week after the neuroimaging session. Results Increased activity in neural systems associated with the distress of social exclusion and mentalizing during an exclusion episode predicted increased risk taking in the presence of a peer (controlling for solo risk behavior) during a driving simulator session outside of the neuroimaging lab one week later. These neural measures predicted risky driving behavior above and beyond self-reports of susceptibility to peer pressure and distress during exclusion. Conclusions These results speak to the neural bases of social influence and risk taking; contribute to our understanding of social and emotional function in the adolescent brain; and link neural activity in specific, hypothesized, regions to risk-relevant outcomes beyond the neuroimaging lab. Results of this investigation are discussed in terms of the mechanisms underlying risk taking in adolescents and the public health implications for adolescent driving. PMID:24759437

  14. Neural tube closure depends on expression of Grainyhead-like 3 in multiple tissues.

    PubMed

    De Castro, Sandra C P; Hirst, Caroline S; Savery, Dawn; Rolo, Ana; Lickert, Heiko; Andersen, Bogi; Copp, Andrew J; Greene, Nicholas D E

    2018-03-15

    Failure of neural tube closure leads to neural tube defects (NTDs), common congenital abnormalities in humans. Among the genes whose loss of function causes NTDs in mice, Grainyhead-like3 (Grhl3) is essential for spinal neural tube closure, with null mutants exhibiting fully penetrant spina bifida. During spinal neurulation Grhl3 is initially expressed in the surface (non-neural) ectoderm, subsequently in the neuroepithelial component of the neural folds and at the node-streak border, and finally in the hindgut endoderm. Here, we show that endoderm-specific knockout of Grhl3 causes late-arising spinal NTDs, preceded by increased ventral curvature of the caudal region which was shown previously to suppress closure of the spinal neural folds. This finding supports the hypothesis that diminished Grhl3 expression in the hindgut is the cause of spinal NTDs in the curly tail, carrying a hypomorphic Grhl3 allele. Complete loss of Grhl3 function produces a more severe phenotype in which closure fails earlier in neurulation, before the stage of onset of expression in the hindgut of wild-type embryos. This implicates additional tissues and NTD mechanisms in Grhl3 null embryos. Conditional knockout of Grhl3 in the neural plate and node-streak border has minimal effect on closure, suggesting that abnormal function of surface ectoderm, where Grhl3 transcripts are first detected, is primarily responsible for early failure of spinal neurulation in Grhl3 null embryos. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Neural activation patterns during response inhibition distinguish adolescents with ADHD, their unaffected siblings, and healthy controls

    PubMed Central

    van Rooij, Daan; Hoekstra, Pieter J.; Mennes, Maarten; von Rhein, Daniel; Thissen, Andrieke J.A.M.; Heslenfeld, Dirk; Zwiers, Marcel P.; Faraone, Stephen V.; Oosterlaan, Jaap; Franke, Barbara; Rommelse, Nanda; Buitelaar, Jan K.; Hartman, Catharina A.

    2015-01-01

    Objective Impaired response inhibition is a key executive function deficit of attention-deficit/hyperactivity disorder (ADHD). Still, behavioral response inhibition measures do not consistently differentiate individuals with ADHD from unaffected individuals. We therefore investigated the neural correlates of response inhibition as well as the familial nature of these neural correlates. Methods fMRI measurements of neural activation during the stop-signal task along with behavioral measures of response inhibition were obtained in adolescents and young adults with ADHD (N=185), their unaffected siblings (N=111), and healthy controls (N=124). Results Stop-signal reaction times were longer in participants with ADHD, but not in their unaffected siblings, while reaction time variability and error rates were higher in both groups than in controls. Neural hypoactivation was observed in frontal-striatal and frontal-parietal networks of participants with ADHD and unaffected siblings compared to controls, whereby activation in inferior frontal and temporal/parietal nodes in unaffected siblings was intermediate between that of participants with ADHD and controls. Furthermore, neural activation in inferior frontal nodes correlated with stop-signal reaction times, and activation in both inferior frontal and temporal/parietal nodes correlated with ADHD severity. Conclusions Neural activation alterations in ADHD are more robust than behavioral response inhibition deficits and explain variance in response inhibition and ADHD severity. Although only affected participants with ADHD have deficient response inhibition, hypoactivation in inferior frontal and temporal-parietal nodes in unaffected siblings support the familial nature of the underlying neural process. Hypoactivation in these nodes may be useful as endophenotypes that extend beyond the affected individuals in the family. PMID:25615565

  16. Auditory Responses to Electric and Infrared Neural Stimulation of the Rat Cochlear Nucleus

    PubMed Central

    Verma, Rohit; Guex, Amelie A.; Hancock, Kenneth E.; Durakovic, Nedim; McKay, Colette M.; Slama, Michaël C. C.; Brown, M. Christian; Lee, Daniel J.

    2014-01-01

    In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported “optophonic” effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. PMID:24508368

  17. Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls.

    PubMed

    Neumeister, Alexander; Nugent, Allison C; Waldeck, Tracy; Geraci, Marilla; Schwarz, Markus; Bonne, Omer; Bain, Earle E; Luckenbaugh, David A; Herscovitch, Peter; Charney, Dennis S; Drevets, Wayne C

    2004-08-01

    An instructive paradigm for investigating the relationship between brain serotonin function and major depressive disorder (MDD) is the response to tryptophan depletion (TD) induced by oral loading with all essential amino acids except the serotonin precursor tryptophan. To determine whether serotonin dysfunction represents a trait abnormality in MDD in the context of specific neural circuitry abnormalities involved in the pathogenesis of MDD. Randomized double-blind crossover study. Outpatient clinic. Twenty-seven medication-free patients with remitted MDD (18 women and 9 men; mean +/- SD age, 39.8 +/- 12.7 years) and 19 controls (10 women and 9 men; mean +/- SD age, 34.4 +/- 11.5 years). We induced TD by administering capsules containing an amino acid mixture without tryptophan. Sham depletion used identical capsules containing hydrous lactose. Fluorodeoxyglucose F 18 positron emission tomography studies were performed 6 hours after TD. Magnetic resonance images were obtained for all participants. Quantitative positron emission tomography of regional cerebral glucose utilization to study the neural effects of sham depletion and TD. Behavioral assessments used a modified (24-item) version of the Hamilton Depression Rating Scale. Tryptophan depletion induced a transient return of depressive symptoms in patients with remitted MDD but not in controls (P<.001). Compared with sham depletion, TD was associated with an increase in regional cerebral glucose utilization in the orbitofrontal cortex, medial thalamus, anterior and posterior cingulate cortices, and ventral striatum in patients with remitted MDD but not in controls. The pattern of TD-induced regional cerebral glucose utilization changes in patients with remitted MDD suggests that TD unmasks a disease-specific, serotonin system-related trait dysfunction and identifies a circuit that probably plays a key role in the pathogenesis of MDD.

  18. Differences in neural responses to ipsilateral stimuli in wide-view fields between face- and house-selective areas

    PubMed Central

    Li, Ting; Niu, Yan; Xiang, Jie; Cheng, Junjie; Liu, Bo; Zhang, Hui; Yan, Tianyi; Kanazawa, Susumu; Wu, Jinglong

    2018-01-01

    Category-selective brain areas exhibit varying levels of neural activity to ipsilaterally presented stimuli. However, in face- and house-selective areas, the neural responses evoked by ipsilateral stimuli in the peripheral visual field remain unclear. In this study, we displayed face and house images using a wide-view visual presentation system while performing functional magnetic resonance imaging (fMRI). The face-selective areas (fusiform face area (FFA) and occipital face area (OFA)) exhibited intense neural responses to ipsilaterally presented images, whereas the house-selective areas (parahippocampal place area (PPA) and transverse occipital sulcus (TOS)) exhibited substantially smaller and even negative neural responses to the ipsilaterally presented images. We also found that the category preferences of the contralateral and ipsilateral neural responses were similar. Interestingly, the face- and house-selective areas exhibited neural responses to ipsilateral images that were smaller than the responses to the contralateral images. Multi-voxel pattern analysis (MVPA) was implemented to evaluate the difference between the contralateral and ipsilateral responses. The classification accuracies were much greater than those expected by chance. The classification accuracies in the FFA were smaller than those in the PPA and TOS. The closer eccentricities elicited greater classification accuracies in the PPA and TOS. We propose that these ipsilateral neural responses might be interpreted by interhemispheric communication through intrahemispheric connectivity of white matter connection and interhemispheric connectivity via the corpus callosum and occipital white matter connection. Furthermore, the PPA and TOS likely have weaker interhemispheric communication than the FFA and OFA, particularly in the peripheral visual field. PMID:29451872

  19. Targeting Neural Synchrony Deficits is Sufficient to Improve Cognition in a Schizophrenia-Related Neurodevelopmental Model

    PubMed Central

    Lee, Heekyung; Dvorak, Dino; Fenton, André A.

    2014-01-01

    Cognitive symptoms are core features of mental disorders but procognitive treatments are limited. We have proposed a “discoordination” hypothesis that cognitive impairment results from aberrant coordination of neural activity. We reported that neonatal ventral hippocampus lesion (NVHL) rats, an established neurodevelopmental model of schizophrenia, have abnormal neural synchrony and cognitive deficits in the active place avoidance task. During stillness, we observed that cortical local field potentials sometimes resembled epileptiform spike-wave discharges with higher prevalence in NVHL rats, indicating abnormal neural synchrony due perhaps to imbalanced excitation–inhibition coupling. Here, within the context of the hypothesis, we investigated whether attenuating abnormal neural synchrony will improve cognition in NVHL rats. We report that: (1) inter-hippocampal synchrony in the theta and beta bands is correlated with active place avoidance performance; (2) the anticonvulsant ethosuximide attenuated the abnormal spike-wave activity, improved cognitive control, and reduced hyperlocomotion; (3) ethosuximide not only normalized the task-associated theta and beta synchrony between the two hippocampi but also increased synchrony between the medial prefrontal cortex and hippocampus above control levels; (4) the antipsychotic olanzapine was less effective at improving cognitive control and normalizing place avoidance-related inter-hippocampal neural synchrony, although it reduced hyperactivity; and (5) olanzapine caused an abnormal pattern of frequency-independent increases in neural synchrony, in both NVHL and control rats. These data suggest that normalizing aberrant neural synchrony can be beneficial and that drugs targeting the pathophysiology of abnormally coordinated neural activities may be a promising theoretical framework and strategy for developing treatments that improve cognition in neurodevelopmental disorders such as schizophrenia. PMID:24592242

  20. Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals

    PubMed Central

    Kardava, Lela; Moir, Susan; Shah, Naisha; Wang, Wei; Wilson, Richard; Buckner, Clarisa M.; Santich, Brian H.; Kim, Leo J.Y.; Spurlin, Emily E.; Nelson, Amy K.; Wheatley, Adam K.; Harvey, Christopher J.; McDermott, Adrian B.; Wucherpfennig, Kai W.; Chun, Tae-Wook; Tsang, John S.; Li, Yuxing; Fauci, Anthony S.

    2014-01-01

    Recently, several neutralizing anti-HIV antibodies have been isolated from memory B cells of HIV-infected individuals. Despite extensive evidence of B cell dysfunction in HIV disease, little is known about the cells from which these rare HIV-specific antibodies originate. Accordingly, we used HIV envelope gp140 and CD4 or coreceptor (CoR) binding site (bs) mutant probes to evaluate HIV-specific responses in peripheral blood B cells of HIV-infected individuals at various stages of infection. In contrast to non-HIV responses, HIV-specific responses against gp140 were enriched within abnormal B cells, namely activated and exhausted memory subsets, which are largely absent in the blood of uninfected individuals. Responses against the CoRbs, which is a poorly neutralizing epitope, arose early, whereas those against the well-characterized neutralizing epitope CD4bs were delayed and infrequent. Enrichment of the HIV-specific response within resting memory B cells, the predominant subset in uninfected individuals, did occur in certain infected individuals who maintained low levels of plasma viremia and immune activation with or without antiretroviral therapy. The distribution of HIV-specific responses among memory B cell subsets was corroborated by transcriptional analyses. Taken together, our findings provide valuable insight into virus-specific B cell responses in HIV infection and demonstrate that memory B cell abnormalities may contribute to the ineffectiveness of the antibody response in infected individuals. PMID:24892810

  1. A computational relationship between thalamic sensory neural responses and contrast perception.

    PubMed

    Jiang, Yaoguang; Purushothaman, Gopathy; Casagrande, Vivien A

    2015-01-01

    Uncovering the relationship between sensory neural responses and perceptual decisions remains a fundamental problem in neuroscience. Decades of experimental and modeling work in the sensory cortex have demonstrated that a perceptual decision pool is usually composed of tens to hundreds of neurons, the responses of which are significantly correlated not only with each other, but also with the behavioral choices of an animal. Few studies, however, have measured neural activity in the sensory thalamus of awake, behaving animals. Therefore, it remains unclear how many thalamic neurons are recruited and how the information from these neurons is pooled at subsequent cortical stages to form a perceptual decision. In a previous study we measured neural activity in the macaque lateral geniculate nucleus (LGN) during a two alternative forced choice (2AFC) contrast detection task, and found that single LGN neurons were significantly correlated with the monkeys' behavioral choices, despite their relatively poor contrast sensitivity and a lack of overall interneuronal correlations. We have now computationally tested a number of specific hypotheses relating these measured LGN neural responses to the contrast detection behavior of the animals. We modeled the perceptual decisions with different numbers of neurons and using a variety of pooling/readout strategies, and found that the most successful model consisted of about 50-200 LGN neurons, with individual neurons weighted differentially according to their signal-to-noise ratios (quantified as d-primes). These results supported the hypothesis that in contrast detection the perceptual decision pool consists of multiple thalamic neurons, and that the response fluctuations in these neurons can influence contrast perception, with the more sensitive thalamic neurons likely to exert a greater influence.

  2. Abnormal activity in reward brain circuits in human narcolepsy with cataplexy.

    PubMed

    Ponz, Aurélie; Khatami, Ramin; Poryazova, Rositsa; Werth, Esther; Boesiger, Peter; Bassetti, Claudio L; Schwartz, Sophie

    2010-02-01

    Hypothalamic hypocretins (or orexins) regulate energy metabolism and arousal maintenance. Recent animal research suggests that hypocretins may also influence reward-related behaviors. In humans, the loss of hypocretin-containing neurons results in a major sleep-wake disorder called narcolepsy-cataplexy, which is associated with emotional disturbances. Here, we aim to test whether narcoleptic patients show an abnormal pattern of brain activity during reward processing. We used functional magnetic resonance imaging in 12 unmedicated patients with narcolepsy-cataplexy to measure the neural responses to expectancy and experience of monetary gains and losses. We statistically compared the patients' data with those obtained in a group of 12 healthy matched controls. Our results reveal that activity in the dopaminergic ventral midbrain (ventral tegmental area) was not modulated in narcolepsy-cataplexy patients during high reward expectancy (unlike controls), and that ventral striatum activity was reduced during winning. By contrast, the patients showed abnormal activity increases in the amygdala and in dorsal striatum for positive outcomes. In addition, we found that activity in the nucleus accumbens and the ventral-medial prefrontal cortex correlated with disease duration, suggesting that an alternate neural circuit could be privileged over the years to control affective responses to emotional challenges and compensate for the lack of influence from ventral midbrain regions. Our study offers a detailed picture of the distributed brain network involved during distinct stages of reward processing and shows for the first time, to our knowledge, how this network is affected in hypocretin-deficient narcoleptic patients.

  3. Associations between maternal negative affect and adolescent's neural response to peer evaluation

    PubMed Central

    Tan, Patricia Z.; Lee, Kyung Hwa; Dahl, Ronald E.; Nelson, Eric E.; Stroud, Laura J.; Siegle, Greg J.; Morgan, Judith K.; Silk, Jennifer S.

    2016-01-01

    Parenting is often implicated as a potential source of individual differences in youths’ emotional information processing. The present study examined whether parental affect is related to an important aspect of adolescent emotional development, response to peer evaluation. Specifically, we examined relations between maternal negative affect, observed during parent–adolescent discussion of an adolescent-nominated concern with which s/he wants parental support, and adolescent neural responses to peer evaluation in 40 emotionally healthy and depressed adolescents. We focused on a network of ventral brain regions involved in affective processing of social information: the amygdala, anterior insula, nucleus accumbens, and subgenual anterior cingulate, as well as the ventrolateral prefrontal cortex. Maternal negative affect was not associated with adolescent neural response to peer rejection. However, longer durations of maternal negative affect were associated with decreased responsivity to peer acceptance in the amygdala, left anterior insula, subgenual anterior cingulate, and left nucleus accumbens. These findings provide some of the first evidence that maternal negative affect is associated with adolescents’ neural processing of social rewards. Findings also suggest that maternal negative affect could contribute to alterations in affective processing, specifically, dampening the saliency and/or reward of peer interactions during adolescence. PMID:24613174

  4. Dissociable neural response signatures for slow amplitude and frequency modulation in human auditory cortex.

    PubMed

    Henry, Molly J; Obleser, Jonas

    2013-01-01

    Natural auditory stimuli are characterized by slow fluctuations in amplitude and frequency. However, the degree to which the neural responses to slow amplitude modulation (AM) and frequency modulation (FM) are capable of conveying independent time-varying information, particularly with respect to speech communication, is unclear. In the current electroencephalography (EEG) study, participants listened to amplitude- and frequency-modulated narrow-band noises with a 3-Hz modulation rate, and the resulting neural responses were compared. Spectral analyses revealed similar spectral amplitude peaks for AM and FM at the stimulation frequency (3 Hz), but amplitude at the second harmonic frequency (6 Hz) was much higher for FM than for AM. Moreover, the phase delay of neural responses with respect to the full-band stimulus envelope was shorter for FM than for AM. Finally, the critical analysis involved classification of single trials as being in response to either AM or FM based on either phase or amplitude information. Time-varying phase, but not amplitude, was sufficient to accurately classify AM and FM stimuli based on single-trial neural responses. Taken together, the current results support the dissociable nature of cortical signatures of slow AM and FM. These cortical signatures potentially provide an efficient means to dissect simultaneously communicated slow temporal and spectral information in acoustic communication signals.

  5. Relation of obesity to neural activation in response to food commercials.

    PubMed

    Gearhardt, Ashley N; Yokum, Sonja; Stice, Eric; Harris, Jennifer L; Brownell, Kelly D

    2014-07-01

    Adolescents view thousands of food commercials annually, but the neural response to food advertising and its association with obesity is largely unknown. This study is the first to examine how neural response to food commercials differs from other stimuli (e.g. non-food commercials and television show) and to explore how this response may differ by weight status. The blood oxygen level-dependent functional magnetic resonance imaging activation was measured in 30 adolescents ranging from lean to obese in response to food and non-food commercials imbedded in a television show. Adolescents exhibited greater activation in regions implicated in visual processing (e.g. occipital gyrus), attention (e.g. parietal lobes), cognition (e.g. temporal gyrus and posterior cerebellar lobe), movement (e.g. anterior cerebellar cortex), somatosensory response (e.g. postcentral gyrus) and reward [e.g. orbitofrontal cortex and anterior cingulate cortex (ACC)] during food commercials. Obese participants exhibited less activation during food relative to non-food commercials in neural regions implicated in visual processing (e.g. cuneus), attention (e.g. posterior cerebellar lobe), reward (e.g. ventromedial prefrontal cortex and ACC) and salience detection (e.g. precuneus). Obese participants did exhibit greater activation in a region implicated in semantic control (e.g. medial temporal gyrus). These findings may inform current policy debates regarding the impact of food advertising to minors. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  6. Emotional withdrawal, CT abnormalities and drug response in late life depression.

    PubMed

    Altamura, A Carlo; Bassetti, Roberta; Santini, Annalisa; Frisoni, G B; Mundo, Emanuela

    2004-03-01

    In this study, the authors investigated if CNS degenerative abnormalities could correlate with depressive symptoms in elderly patients, if the presence of mild/moderate cognitive impairment could be related to the response to treatment and the role of peculiar clinical features in influencing the response to treatment. Fifty-three patients (60-75 years) diagnosed as affected by late onset (after 60 years) Major Depressive Episodes according to DSM-IV criteria were studied. Brain vascular and degenerative markers were assessed by computed tomography (CT) through measurements of a lateralized version of the bifrontal index and a rating scale addressing subcortical disease. The presence of mild/moderate cognitive impairment [(24-28 total score at the Mini-Mental State Examination (MMSE)], and of specific symptoms were assessed at baseline and evaluated with respect to the antidepressant response. Patients with CT abnormalities showed higher baseline scores on Hamilton Rating Scale for Depression (HAM-D) items "late insomnia" (t=-2.674, P=.002), "somatic symptoms" (t=-3.355 P=.002), and Brief Psychiatric Rating Scale (BPRS) item "emotional withdrawal" (t=-3.355, P=.002). No significant correlation was found between the vascular index and baseline clinical symptoms, while the HAM-D "depressed mood" item was negatively correlated to the right frontal index (R=-0.692, P=.006). Patients with CT abnormalities showed a lower reduction of HAM-D total scores than patients with normal CT (time effect: F=29.277, P<.0001; group effect: F=5.154, P<.03), while a significant reduction of symptoms in time (time effect: F=33.33, P<.0001) but no differences between groups were found on Hamilton Rating Scale for Anxiety (HAM-A). Both patients with and without mild cognitive impairment improved on the HAM-D (time effect: F=19.668, P<.0001), BPRS (time effect: F=18.345, P<.0001), and HAM-A (time effect: F=17.959, P<.0001) total scores. Patients with emotional withdrawal showed lower

  7. Analyzing neural responses with vector fields.

    PubMed

    Buneo, Christopher A

    2011-04-15

    Analyzing changes in the shape and scale of single cell response fields is a key component of many neurophysiological studies. Typical analyses of shape change involve correlating firing rates between experimental conditions or "cross-correlating" single cell tuning curves by shifting them with respect to one another and correlating the overlapping data. Such shifting results in a loss of data, making interpretation of the resulting correlation coefficients problematic. The problem is particularly acute for two dimensional response fields, which require shifting along two axes. Here, an alternative method for quantifying response field shape and scale based on correlation of vector field representations is introduced. The merits and limitations of the methods are illustrated using both simulated and experimental data. It is shown that vector correlation provides more information on response field changes than scalar correlation without requiring field shifting and concomitant data loss. An extension of this vector field approach is also demonstrated which can be used to identify the manner in which experimental variables are encoded in studies of neural reference frames. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Neural responses to salient visual stimuli.

    PubMed Central

    Morris, J S; Friston, K J; Dolan, R J

    1997-01-01

    The neural mechanisms involved in the selective processing of salient or behaviourally important stimuli are uncertain. We used an aversive conditioning paradigm in human volunteer subjects to manipulate the salience of visual stimuli (emotionally expressive faces) presented during positron emission tomography (PET) neuroimaging. Increases in salience, and conflicts between the innate and acquired value of the stimuli, produced augmented activation of the pulvinar nucleus of the right thalamus. Furthermore, this pulvinar activity correlated positively with responses in structures hypothesized to mediate value in the brain right amygdala and basal forebrain (including the cholinergic nucleus basalis of Meynert). The results provide evidence that the pulvinar nucleus of the thalamus plays a crucial modulatory role in selective visual processing, and that changes in perceptual salience are mediated by value-dependent plasticity in pulvinar responses. PMID:9178546

  9. Neural code alterations and abnormal time patterns in Parkinson’s disease

    NASA Astrophysics Data System (ADS)

    Andres, Daniela Sabrina; Cerquetti, Daniel; Merello, Marcelo

    2015-04-01

    Objective. The neural code used by the basal ganglia is a current question in neuroscience, relevant for the understanding of the pathophysiology of Parkinson’s disease. While a rate code is known to participate in the communication between the basal ganglia and the motor thalamus/cortex, different lines of evidence have also favored the presence of complex time patterns in the discharge of the basal ganglia. To gain insight into the way the basal ganglia code information, we studied the activity of the globus pallidus pars interna (GPi), an output node of the circuit. Approach. We implemented the 6-hydroxydopamine model of Parkinsonism in Sprague-Dawley rats, and recorded the spontaneous discharge of single GPi neurons, in head-restrained conditions at full alertness. Analyzing the temporal structure function, we looked for characteristic scales in the neuronal discharge of the GPi. Main results. At a low-scale, we observed the presence of dynamic processes, which allow the transmission of time patterns. Conversely, at a middle-scale, stochastic processes force the use of a rate code. Regarding the time patterns transmitted, we measured the word length and found that it is increased in Parkinson’s disease. Furthermore, it showed a positive correlation with the frequency of discharge, indicating that an exacerbation of this abnormal time pattern length can be expected, as the dopamine depletion progresses. Significance. We conclude that a rate code and a time pattern code can co-exist in the basal ganglia at different temporal scales. However, their normal balance is progressively altered and replaced by pathological time patterns in Parkinson’s disease.

  10. Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia.

    PubMed

    Kita, Hitoshi; Kita, Takako

    2011-07-13

    The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

  11. Quantifying the signals contained in heterogeneous neural responses and determining their relationships with task performance

    PubMed Central

    Pagan, Marino

    2014-01-01

    The responses of high-level neurons tend to be mixtures of many different types of signals. While this diversity is thought to allow for flexible neural processing, it presents a challenge for understanding how neural responses relate to task performance and to neural computation. To address these challenges, we have developed a new method to parse the responses of individual neurons into weighted sums of intuitive signal components. Our method computes the weights by projecting a neuron's responses onto a predefined orthonormal basis. Once determined, these weights can be combined into measures of signal modulation; however, in their raw form these signal modulation measures are biased by noise. Here we introduce and evaluate two methods for correcting this bias, and we report that an analytically derived approach produces performance that is robust and superior to a bootstrap procedure. Using neural data recorded from inferotemporal cortex and perirhinal cortex as monkeys performed a delayed-match-to-sample target search task, we demonstrate how the method can be used to quantify the amounts of task-relevant signals in heterogeneous neural populations. We also demonstrate how these intuitive quantifications of signal modulation can be related to single-neuron measures of task performance (d′). PMID:24920017

  12. Neuroendocrine abnormalities in hypothalamic amenorrhea: spectrum, stability, and response to neurotransmitter modulation.

    PubMed

    Perkins, R B; Hall, J E; Martin, K A

    1999-06-01

    To characterize the neuroendocrine patterns of abnormal GnRH secretion in hypothalamic amenorrhea (HA), 49 women with primary and secondary HA underwent frequent sampling of LH in a total of 72 baseline studies over 12-24 h. A subset of women participated in more than one study to address 1) the variability of LH pulse patterns over time; and 2) the impact of modulating opioid, dopaminergic, and adrenergic tone on LH secretory patterns. The frequency and amplitude of LH secretion was compared with that seen in the early follicular phase (EFP) of normally cycling women. The spectrum of abnormalities of LH pulses was 8% apulsatile, 27% low frequency/low amplitude, 8% low amplitude/normal frequency, 43% low frequency/normal amplitude, 14% normal frequency/normal amplitude. Of patients studied overnight, 45% demonstrated a pubertal pattern of augmented LH secretion during sleep. Of patients studied repeatedly, 75% demonstrated at least 2 different patterns of LH secretion, and 33% reverted at least once to a normal pattern of secretion. An increase in LH pulse frequency was seen in 12 of 15 subjects in response to naloxone (opioid receptor antagonist). Clonidine (alpha-2 adrenergic agonist) was associated with a decrease in mean LH in 3 of 3 subjects. An increase in LH pulse frequency was seen in 4 of 8 subjects in response to metoclopramide (dopamine receptor antagonist), but the response was not statistically significant. Baseline abnormalities in LH secretion did not appear to influence response to neurotransmitter modulation. 1) HA represents a spectrum of disordered GnRH secretion that can vary over time; 2) LH pulse patterns at baseline do not appear to influence the ability to respond to neurotransmitter modulation; 3) Opioid and adrenergic tone appear to influence the hypothalamic GnRH pulse generator in some individuals with HA.

  13. Auditory responses to electric and infrared neural stimulation of the rat cochlear nucleus.

    PubMed

    Verma, Rohit U; Guex, Amélie A; Hancock, Kenneth E; Durakovic, Nedim; McKay, Colette M; Slama, Michaël C C; Brown, M Christian; Lee, Daniel J

    2014-04-01

    In an effort to improve the auditory brainstem implant, a prosthesis in which user outcomes are modest, we applied electric and infrared neural stimulation (INS) to the cochlear nucleus in a rat animal model. Electric stimulation evoked regions of neural activation in the inferior colliculus and short-latency, multipeaked auditory brainstem responses (ABRs). Pulsed INS, delivered to the surface of the cochlear nucleus via an optical fiber, evoked broad neural activation in the inferior colliculus. Strongest responses were recorded when the fiber was placed at lateral positions on the cochlear nucleus, close to the temporal bone. INS-evoked ABRs were multipeaked but longer in latency than those for electric stimulation; they resembled the responses to acoustic stimulation. After deafening, responses to electric stimulation persisted, whereas those to INS disappeared, consistent with a reported "optophonic" effect, a laser-induced acoustic artifact. Thus, for deaf individuals who use the auditory brainstem implant, INS alone did not appear promising as a new approach. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Clozapine-induced EEG abnormalities and clinical response to clozapine.

    PubMed

    Risby, E D; Epstein, C M; Jewart, R D; Nguyen, B V; Morgan, W N; Risch, S C; Thrivikraman, K V; Lewine, R L

    1995-01-01

    The authors hypothesized that patients who develop gross EEG abnormalities during clozapine treatment would have a less favorable outcome than patients who did not develop abnormal EEGs. The clinical EEGs and the Brief Psychiatric Rating Scale (BPRS) scores of 12 patients with schizophrenia and 4 patients with schizoaffective disorder were compared before and during treatment with clozapine. Eight patients developed significant EEG abnormalities on clozapine; 1 showed worsening of an abnormal pre-clozapine EEG; none of these subjects had clinical seizures. BPRS scores improved significantly in the group of patients who developed abnormal EEGs but not in the group who did not. Findings are consistent with previous reports of a high incidence of clozapine-induced EEG abnormalities and a positive association between these abnormalities and clinical improvement.

  15. Abnormal stress responsivity in a rodent developmental disruption model of schizophrenia.

    PubMed

    Zimmerman, Eric C; Bellaire, Mark; Ewing, Samuel G; Grace, Anthony A

    2013-10-01

    Although numerous studies have implicated stress in the pathophysiology of schizophrenia, less is known about how the effects of stress interact with genetic, developmental, and/or environmental determinants to promote disease progression. In particular, it has been proposed that in humans, stress exposure in adolescence could combine with a predisposition towards increased stress sensitivity, leading to prodromal symptoms and eventually psychosis. However, the neurobiological substrates for this interaction are not fully characterized. Previous work in our lab has demonstrated that rats born to dams administered with the DNA-methylating agent methylazoxymethanol acetate (MAM) at gestational day 17 exhibit as adults behavioral and anatomical abnormalities consistent with those observed in patients with schizophrenia. Here, we examined behavioral and neuroendocrine responses to stress in the MAM model of schizophrenia. MAM-treated male rats were exposed to acute and repeated footshock stress at prepubertal, peripubteral, and adult ages. Ultrasonic vocalizations (USVs), freezing, and corticosterone responses were quantified. We found that juvenile MAM-treated rats emitted significantly more calls, spent more time vocalizing, emitted calls at a higher rate, and showed more freezing in response to acute footshock stress when compared with their saline (SAL) treated counterparts, and that this difference is not present in older animals. In addition, adolescent MAM-treated animals displayed a blunted HPA axis corticosterone response to acute footshock that did not adapt after 10 days of stress exposure. These data demonstrate abnormal stress responsivity in the MAM model of schizophrenia and suggest that these animals are more sensitive to the effects of stress in youth.

  16. Task modulations of racial bias in neural responses to others' suffering.

    PubMed

    Sheng, Feng; Liu, Qiang; Li, Hong; Fang, Fang; Han, Shihui

    2014-03-01

    Recent event related brain potential research observed a greater frontal activity to pain expressions of racial in-group than out-group members and such racial bias in neural responses to others' suffering was modulated by task demands that emphasize race identity or painful feeling. However, as pain expressions activate multiple brain regions in the pain matrix, it remains unclear which part of the neural circuit in response to others' suffering undergoes modulations by task demands. We scanned Chinese adults, using functional MRI, while they categorized Asian and Caucasian faces with pain or neutral expressions in terms of race or identified painful feelings of each individual face. We found that pain vs. neutral expressions of Asian but not Caucasian faces activated the anterior cingulate (ACC) and anterior insular (AI) activity during race judgments. However, pain compared to race judgments increased ACC and AI activity to pain expressions of Caucasian but not Asian faces. Moreover, race judgments induced increased activity in the dorsal medial prefrontal cortex whereas pain judgments increased activity in the bilateral temporoparietal junction. The results suggest that task demands emphasizing an individual's painful feeling increase ACC/AI activities to pain expressions of racial out-group members and reduce the racial bias in empathic neural responses. © 2013.

  17. Neural Reactivity to Angry Faces Predicts Treatment Response in Pediatric Anxiety.

    PubMed

    Bunford, Nora; Kujawa, Autumn; Fitzgerald, Kate D; Swain, James E; Hanna, Gregory L; Koschmann, Elizabeth; Simpson, David; Connolly, Sucheta; Monk, Christopher S; Phan, K Luan

    2017-02-01

    Although cognitive-behavioral psychotherapy (CBT) and pharmacotherapy are evidence-based treatments for pediatric anxiety, many youth with anxiety disorders fail to respond to these treatments. Given limitations of clinical measures in predicting treatment response, identifying neural predictors is timely. In this study, 35 anxious youth (ages 7-19 years) completed an emotional face-matching task during which the late positive potential (LPP), an event-related potential (ERP) component that indexes sustained attention towards emotional stimuli, was measured. Following the ERP measurement, youth received CBT or selective serotonin reuptake inhibitor (SSRI) treatment, and the LPP was examined as a predictor of treatment response. Findings indicated that, accounting for pre-treatment anxiety severity, neural reactivity to emotional faces predicted anxiety severity post- CBT and SSRI treatment such that enhanced electrocortical response to angry faces was associated with better treatment response. An enhanced LPP to angry faces may predict treatment response insofar as it may reflect greater emotion dysregulation or less avoidance and/or enhanced engagement with environmental stimuli in general, including with treatment.

  18. Neural Reactivity to Angry Faces Predicts Treatment Response in Pediatric Anxiety

    PubMed Central

    Kujawa, Autumn; Fitzgerald, Kate D.; Swain, James E.; Hanna, Gregory L.; Koschmann, Elizabeth; Simpson, David; Connolly, Sucheta; Monk, Christopher S.; Phan, K. Luan

    2018-01-01

    Although cognitive-behavioral psychotherapy (CBT) and pharmacotherapy are evidence-based treatments for pediatric anxiety, many youth with anxiety disorders fail to respond to these treatments. Given limitations of clinical measures in predicting treatment response, identifying neural predictors is timely. In this study, 35 anxious youth (ages 7–19 years) completed an emotional face-matching task during which the late positive potential (LPP), an event-related potential (ERP) component that indexes sustained attention towards emotional stimuli, was measured. Following the ERP measurement, youth received CBT or selective serotonin reuptake inhibitor (SSRI) treatment, and the LPP was examined as a predictor of treatment response. Findings indicated that, accounting for pre-treatment anxiety severity, neural reactivity to emotional faces predicted anxiety severity post-CBT and SSRI treatment such that enhanced electrocortical response to angry faces was associated with better treatment response. An enhanced LPP to angry faces may predict treatment response insofar as it may reflect greater emotion dysregulation or less avoidance and/or enhanced engagement with environmental stimuli in general, including with treatment. PMID:27255517

  19. Fitting of dynamic recurrent neural network models to sensory stimulus-response data.

    PubMed

    Doruk, R Ozgur; Zhang, Kechen

    2018-06-02

    We present a theoretical study aiming at model fitting for sensory neurons. Conventional neural network training approaches are not applicable to this problem due to lack of continuous data. Although the stimulus can be considered as a smooth time-dependent variable, the associated response will be a set of neural spike timings (roughly the instants of successive action potential peaks) that have no amplitude information. A recurrent neural network model can be fitted to such a stimulus-response data pair by using the maximum likelihood estimation method where the likelihood function is derived from Poisson statistics of neural spiking. The universal approximation feature of the recurrent dynamical neuron network models allows us to describe excitatory-inhibitory characteristics of an actual sensory neural network with any desired number of neurons. The stimulus data are generated by a phased cosine Fourier series having a fixed amplitude and frequency but a randomly shot phase. Various values of amplitude, stimulus component size, and sample size are applied in order to examine the effect of the stimulus to the identification process. Results are presented in tabular and graphical forms at the end of this text. In addition, to demonstrate the success of this research, a study involving the same model, nominal parameters and stimulus structure, and another study that works on different models are compared to that of this research.

  20. Neural responses to maternal criticism in healthy youth

    PubMed Central

    Siegle, Greg J.; Dahl, Ronald E.; Hooley, Jill M.; Silk, Jennifer S.

    2015-01-01

    Parental criticism can have positive and negative effects on children’s and adolescents’ behavior; yet, it is unclear how youth react to, understand and process parental criticism. We proposed that youth would engage three sets of neural processes in response to parental criticism including the following: (i) activating emotional reactions, (ii) regulating those reactions and (iii) social cognitive processing (e.g. understanding the parent’s mental state). To examine neural processes associated with both emotional and social processing of parental criticism in personally relevant and ecologically valid social contexts, typically developing youth were scanned while they listened to their mother providing critical, praising and neutral statements. In response to maternal criticism, youth showed increased brain activity in affective networks (e.g. subcortical–limbic regions including lentiform nucleus and posterior insula), but decreased activity in cognitive control networks (e.g. dorsolateral prefrontal cortex and caudal anterior cingulate cortex) and social cognitive networks (e.g. temporoparietal junction and posterior cingulate cortex/precuneus). These results suggest that youth may respond to maternal criticism with increased emotional reactivity but decreased cognitive control and social cognitive processing. A better understanding of children’s responses to parental criticism may provide insights into the ways that parental feedback can be modified to be more helpful to behavior and development in youth. PMID:25338632

  1. Dissociable Neural Response Signatures for Slow Amplitude and Frequency Modulation in Human Auditory Cortex

    PubMed Central

    Henry, Molly J.; Obleser, Jonas

    2013-01-01

    Natural auditory stimuli are characterized by slow fluctuations in amplitude and frequency. However, the degree to which the neural responses to slow amplitude modulation (AM) and frequency modulation (FM) are capable of conveying independent time-varying information, particularly with respect to speech communication, is unclear. In the current electroencephalography (EEG) study, participants listened to amplitude- and frequency-modulated narrow-band noises with a 3-Hz modulation rate, and the resulting neural responses were compared. Spectral analyses revealed similar spectral amplitude peaks for AM and FM at the stimulation frequency (3 Hz), but amplitude at the second harmonic frequency (6 Hz) was much higher for FM than for AM. Moreover, the phase delay of neural responses with respect to the full-band stimulus envelope was shorter for FM than for AM. Finally, the critical analysis involved classification of single trials as being in response to either AM or FM based on either phase or amplitude information. Time-varying phase, but not amplitude, was sufficient to accurately classify AM and FM stimuli based on single-trial neural responses. Taken together, the current results support the dissociable nature of cortical signatures of slow AM and FM. These cortical signatures potentially provide an efficient means to dissect simultaneously communicated slow temporal and spectral information in acoustic communication signals. PMID:24205309

  2. Associations between maternal negative affect and adolescent's neural response to peer evaluation.

    PubMed

    Tan, Patricia Z; Lee, Kyung Hwa; Dahl, Ronald E; Nelson, Eric E; Stroud, Laura J; Siegle, Greg J; Morgan, Judith K; Silk, Jennifer S

    2014-04-01

    Parenting is often implicated as a potential source of individual differences in youths' emotional information processing. The present study examined whether parental affect is related to an important aspect of adolescent emotional development, response to peer evaluation. Specifically, we examined relations between maternal negative affect, observed during parent-adolescent discussion of an adolescent-nominated concern with which s/he wants parental support, and adolescent neural responses to peer evaluation in 40 emotionally healthy and depressed adolescents. We focused on a network of ventral brain regions involved in affective processing of social information: the amygdala, anterior insula, nucleus accumbens, and subgenual anterior cingulate, as well as the ventrolateral prefrontal cortex. Maternal negative affect was not associated with adolescent neural response to peer rejection. However, longer durations of maternal negative affect were associated with decreased responsivity to peer acceptance in the amygdala, left anterior insula, subgenual anterior cingulate, and left nucleus accumbens. These findings provide some of the first evidence that maternal negative affect is associated with adolescents' neural processing of social rewards. Findings also suggest that maternal negative affect could contribute to alterations in affective processing, specifically, dampening the saliency and/or reward of peer interactions during adolescence. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Pupillary responses in non-proliferative diabetic retinopathy.

    PubMed

    Park, Jason C; Chen, Yi-Fan; Blair, Norman P; Chau, Felix Y; Lim, Jennifer I; Leiderman, Yannek I; Shahidi, Mahnaz; McAnany, J Jason

    2017-03-23

    The goal of this study was to determine the extent of rod-, cone-, and melanopsin-mediated pupillary light reflex (PLR) abnormalities in diabetic patients who have non-proliferative diabetic retinopathy (NPDR). Fifty diabetic subjects who have different stages of NPDR and 25 age-equivalent, non-diabetic controls participated. PLRs were measured in response to full-field, brief-flash stimuli under conditions that target the rod, cone, and intrinsically-photosensitive (melanopsin) retinal ganglion cell pathways. Pupil responses were compared among the subjects groups using age-corrected linear mixed models. Compared to control, the mean baseline pupil diameters were significantly smaller for all patient groups in the dark (all p < 0.001) and for the moderate-severe NPDR group in the light (p = 0.003). Pairwise comparisons indicated: (1) the mean melanopsin-mediated PLR was significantly reduced in the mild and moderate-severe groups (both p < 0.001); (2) the mean cone-mediated PLR was reduced significantly in the moderate-severe group (p = 0.008); (3) no significant differences in the mean rod-mediated responses. The data indicate abnormalities in NPDR patients under conditions that separately assess pupil function driven by different photoreceptor classes. The results provide evidence for compromised neural function in these patients and provide a promising approach for quantifying their neural abnormalities.

  4. A model of microsaccade-related neural responses induced by short-term depression in thalamocortical synapses

    PubMed Central

    Yuan, Wu-Jie; Dimigen, Olaf; Sommer, Werner; Zhou, Changsong

    2013-01-01

    Microsaccades during fixation have been suggested to counteract visual fading. Recent experiments have also observed microsaccade-related neural responses from cellular record, scalp electroencephalogram (EEG), and functional magnetic resonance imaging (fMRI). The underlying mechanism, however, is not yet understood and highly debated. It has been proposed that the neural activity of primary visual cortex (V1) is a crucial component for counteracting visual adaptation. In this paper, we use computational modeling to investigate how short-term depression (STD) in thalamocortical synapses might affect the neural responses of V1 in the presence of microsaccades. Our model not only gives a possible synaptic explanation for microsaccades in counteracting visual fading, but also reproduces several features in experimental findings. These modeling results suggest that STD in thalamocortical synapses plays an important role in microsaccade-related neural responses and the model may be useful for further investigation of behavioral properties and functional roles of microsaccades. PMID:23630494

  5. Estimating neural response functions from fMRI

    PubMed Central

    Kumar, Sukhbinder; Penny, William

    2014-01-01

    This paper proposes a methodology for estimating Neural Response Functions (NRFs) from fMRI data. These NRFs describe non-linear relationships between experimental stimuli and neuronal population responses. The method is based on a two-stage model comprising an NRF and a Hemodynamic Response Function (HRF) that are simultaneously fitted to fMRI data using a Bayesian optimization algorithm. This algorithm also produces a model evidence score, providing a formal model comparison method for evaluating alternative NRFs. The HRF is characterized using previously established “Balloon” and BOLD signal models. We illustrate the method with two example applications based on fMRI studies of the auditory system. In the first, we estimate the time constants of repetition suppression and facilitation, and in the second we estimate the parameters of population receptive fields in a tonotopic mapping study. PMID:24847246

  6. Method for Constructing Composite Response Surfaces by Combining Neural Networks with other Interpolation or Estimation Techniques

    NASA Technical Reports Server (NTRS)

    Rai, Man Mohan (Inventor); Madavan, Nateri K. (Inventor)

    2003-01-01

    A method and system for design optimization that incorporates the advantages of both traditional response surface methodology (RSM) and neural networks is disclosed. The present invention employs a unique strategy called parameter-based partitioning of the given design space. In the design procedure, a sequence of composite response surfaces based on both neural networks and polynomial fits is used to traverse the design space to identify an optimal solution. The composite response surface has both the power of neural networks and the economy of low-order polynomials (in terms of the number of simulations needed and the network training requirements). The present invention handles design problems with many more parameters than would be possible using neural networks alone and permits a designer to rapidly perform a variety of trade-off studies before arriving at the final design.

  7. Neural Tube Defects

    PubMed Central

    Greene, Nicholas D.E.; Copp, Andrew J.

    2015-01-01

    Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of critical cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies. PMID:25032496

  8. Fault detection and diagnosis using neural network approaches

    NASA Technical Reports Server (NTRS)

    Kramer, Mark A.

    1992-01-01

    Neural networks can be used to detect and identify abnormalities in real-time process data. Two basic approaches can be used, the first based on training networks using data representing both normal and abnormal modes of process behavior, and the second based on statistical characterization of the normal mode only. Given data representative of process faults, radial basis function networks can effectively identify failures. This approach is often limited by the lack of fault data, but can be facilitated by process simulation. The second approach employs elliptical and radial basis function neural networks and other models to learn the statistical distributions of process observables under normal conditions. Analytical models of failure modes can then be applied in combination with the neural network models to identify faults. Special methods can be applied to compensate for sensor failures, to produce real-time estimation of missing or failed sensors based on the correlations codified in the neural network.

  9. Convergent evidence for abnormal striatal synaptic plasticity in dystonia

    PubMed Central

    Peterson, David A.; Sejnowski, Terrence J.; Poizner, Howard

    2010-01-01

    Dystonia is a functionally disabling movement disorder characterized by abnormal movements and postures. Although substantial recent progress has been made in identifying genetic factors, the pathophysiology of the disease remains a mystery. A provocative suggestion gaining broader acceptance is that some aspect of neural plasticity may be abnormal. There is also evidence that, at least in some forms of dystonia, sensorimotor “use” may be a contributing factor. Most empirical evidence of abnormal plasticity in dystonia comes from measures of sensorimotor cortical organization and physiology. However, the basal ganglia also play a critical role in sensorimotor function. Furthermore, the basal ganglia are prominently implicated in traditional models of dystonia, are the primary targets of stereotactic neurosurgical interventions, and provide a neural substrate for sensorimotor learning influenced by neuromodulators. Our working hypothesis is that abnormal plasticity in the basal ganglia is a critical link between the etiology and pathophysiology of dystonia. In this review we set up the background for this hypothesis by integrating a large body of disparate indirect evidence that dystonia may involve abnormalities in synaptic plasticity in the striatum. After reviewing evidence implicating the striatum in dystonia, we focus on the influence of two neuromodulatory systems: dopamine and acetylcholine. For both of these neuromodulators, we first describe the evidence for abnormalities in dystonia and then the means by which it may influence striatal synaptic plasticity. Collectively, the evidence suggests that many different forms of dystonia may involve abnormal plasticity in the striatum. An improved understanding of these altered plastic processes would help inform our understanding of the pathophysiology of dystonia, and, given the role of the striatum in sensorimotor learning, provide a principled basis for designing therapies aimed at the dynamic processes

  10. Neural Responses to Partner Rejection Cues

    PubMed Central

    Zayas, Vivian; Shoda, Yuichi; Mischel, Walter; Osterhout, Lee; Takahashi, Melissa

    2009-01-01

    Little is known about neural responses in the early automatic-stage processing of rejection cues from a partner. Event-related potentials (ERPs) offer a window to study processes that may be difficult to detect via behavioral methods. We focused on the N400 ERP component, which reflects the amount of semantic processing prompted by a target. When participants were primed by attachment-related contexts (“If I need help from my partner, my partner will be …”), rejection-related words (e.g., dismissing) elicited greater N400 amplitudes than acceptance-related words (e.g., supporting). Analyses of results for nonattachment primes suggest that these findings were not simply caused by target valence; the brain responds differentially to cues of partner rejection versus acceptance in under 300 ms. Moreover, these early-stage neurophysiological responses were heightened or dampened as a function of individuals’ adult attachment; women characterized by high anxiety and low avoidance showed the greatest N400 responses to cues of partner rejection (vs. acceptance). PMID:19493321

  11. Neural Response to Reward as a Predictor of Rise in Depressive Symptoms in Adolescence

    PubMed Central

    Morgan, Judith K.; Olino, Thomas M.; McMakin, Dana L.; Ryan, Neal D.; Forbes, Erika E.

    2012-01-01

    Adolescence is a developmental period characterized by significant increases in the onset of depression, but also by increases in depressive symptoms, even among psychiatrically healthy youth. Disrupted reward function has been postulated as a critical factor in the development of depression, but it is still unclear which adolescents are particularly at risk for rising depressive symptoms. We provide a conceptual stance on gender, pubertal development, and reward type as potential moderators of the association between neural response to reward and rises in depressive symptoms. In addition, we describe preliminary findings that support claims of this conceptual stance. We propose that (1) status-related rewards may be particularly salient for eliciting neural response relevant to depressive symptoms in boys, whereas social rewards may be more salient for eliciting neural response relevant to depressive symptoms in girls and (2) the pattern of reduced striatal response and enhanced medial prefrontal response to reward may be particularly predictive of depressive symptoms in pubertal adolescents. We found that greater vmPFC activation when winning rewards predicted greater increases in depressive symptoms over two years, for boys only, and less striatal activation when anticipating rewards predicted greater increases in depressive symptoms over two years, for adolescents in mid to late pubertal stages but not those in pre to early puberty. We also propose directions for future studies, including the investigation of social vs. monetary reward directly and the longitudinal assessment of parallel changes in pubertal development, neural response to reward, and depressive symptoms. PMID:22521464

  12. Fast response and high sensitivity to microsaccades in a cascading-adaptation neural network with short-term synaptic depression

    NASA Astrophysics Data System (ADS)

    Yuan, Wu-Jie; Zhou, Jian-Fang; Zhou, Changsong

    2016-04-01

    Microsaccades are very small eye movements during fixation. Experimentally, they have been found to play an important role in visual information processing. However, neural responses induced by microsaccades are not yet well understood and are rarely studied theoretically. Here we propose a network model with a cascading adaptation including both retinal adaptation and short-term depression (STD) at thalamocortical synapses. In the neural network model, we compare the microsaccade-induced neural responses in the presence of STD and those without STD. It is found that the cascading with STD can give rise to faster and sharper responses to microsaccades. Moreover, STD can enhance response effectiveness and sensitivity to microsaccadic spatiotemporal changes, suggesting improved detection of small eye movements (or moving visual objects). We also explore the mechanism of the response properties in the model. Our studies strongly indicate that STD plays an important role in neural responses to microsaccades. Our model considers simultaneously retinal adaptation and STD at thalamocortical synapses in the study of microsaccade-induced neural activity, and may be useful for further investigation of the functional roles of microsaccades in visual information processing.

  13. Concurrent OCT imaging of stimulus evoked retinal neural activation and hemodynamic responses

    NASA Astrophysics Data System (ADS)

    Son, Taeyoon; Wang, Benquan; Lu, Yiming; Chen, Yanjun; Cao, Dingcai; Yao, Xincheng

    2017-02-01

    It is well established that major retinal diseases involve distortions of the retinal neural physiology and blood vascular structures. However, the details of distortions in retinal neurovascular coupling associated with major eye diseases are not well understood. In this study, a multi-modal optical coherence tomography (OCT) imaging system was developed to enable concurrent imaging of retinal neural activity and vascular hemodynamics. Flicker light stimulation was applied to mouse retinas to evoke retinal neural responses and hemodynamic changes. The OCT images were acquired continuously during the pre-stimulation, light-stimulation, and post-stimulation phases. Stimulus-evoked intrinsic optical signals (IOSs) and hemodynamic changes were observed over time in blood-free and blood regions, respectively. Rapid IOSs change occurred almost immediately after stimulation. Both positive and negative signals were observed in adjacent retinal areas. The hemodynamic changes showed time delays after stimulation. The signal magnitudes induced by light stimulation were observed in blood regions and did not show significant changes in blood-free regions. These differences may arise from different mechanisms in blood vessels and neural tissues in response to light stimulation. These characteristics agreed well with our previous observations in mouse retinas. Further development of the multimodal OCT may provide a new imaging method for studying how retinal structures and metabolic and neural functions are affected by age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and other diseases, which promises novel noninvasive biomarkers for early disease detection and reliable treatment evaluations of eye diseases.

  14. Blunted neural responses to reward in remitted major depression: A high-density event-related potential study

    PubMed Central

    Whitton, Alexis E.; Kakani, Pragya; Foti, Dan; Van’t Veer, Ashlee; Haile, Anja; Crowley, David J.; Pizzagalli, Diego A.

    2015-01-01

    Background Major depressive disorder (MDD) is a highly recurrent condition, and improving our understanding of the abnormalities that persist in remitted MDD (rMDD) may provide insight into mechanisms that contribute to relapse. MDD has been characterized by reward learning deficits linked to dysfunction in frontostriatal regions. Although initial behavioral evidence of reward learning deficits in rMDD has recently emerged, it is unclear whether these reflect impairments in neural reward processing that persist into remission. Methods We examined behavioral reward learning and 128-channel event-related potentials (ERP) during a well-validated probabilistic reward task in 26 rMDD individuals and 34 never-depressed controls. Temporo-spatial principal components analysis (PCA) was used to separate overlapping ERP components, and group differences in neural activity in a priori regions were examined using low-resolution electromagnetic tomography (LORETA). Results Individuals with rMDD displayed reduced behavioral reward learning, as well as blunted ERP amplitude to reward feedback. Importantly, the reduction in ERP amplitude occurred at a PCA factor that peaked during the time at which phasic reward feedback-related signaling – hypothesized to originate in the striatum and project to the anterior cingulate cortex (ACC) – are thought to modulate scalp-recorded activity. Consistent with this, LORETA analyses revealed reduced activity in the ACC in the rMDD group, and this blunting correlated with poorer reward learning. Conclusion These findings suggest that the reward learning impairment observed in acute MDD persists into full remission and that these impairments may be attributable to abnormalities in the neural processes that support reward feedback monitoring, particularly within the ACC. PMID:26858994

  15. Reduced reward-related neural response to mimicry in individuals with autism.

    PubMed

    Hsu, Chun-Ting; Neufeld, Janina; Chakrabarti, Bhismadev

    2018-03-01

    Mimicry is a facilitator of social bonds in humans, from infancy. This facilitation is made possible through changing the reward value of social stimuli; for example, we like and affiliate more with people who mimic us. Autism spectrum disorders (ASD) are marked by difficulties in forming social bonds. In this study, we investigate whether the reward-related neural response to being mimicked is altered in individuals with ASD, using a simple conditioning paradigm. Multiple studies in humans and nonhuman primates have established a crucial role for the ventral striatal (VS) region in responding to rewards. In this study, adults with ASD and matched controls first underwent a conditioning task outside the scanner, where they were mimicked by one face and 'anti-mimicked' by another. In the second part, participants passively viewed the conditioned faces in a 3T MRI scanner using a multi-echo sequence. The differential neural response towards mimicking vs. anti-mimicking faces in the VS was tested for group differences as well as an association with self-reported autistic traits. Multiple regression analysis revealed lower left VS response to mimicry (mimicking > anti-mimicking faces) in the ASD group compared to controls. The VS response to mimicry was negatively correlated with autistic traits across the whole sample. Our results suggest that for individuals with ASD and high autistic traits, being mimicked is associated with lower reward-related neural response. This result points to a potential mechanism underlying the difficulties reported by many of individuals with ASD in building social rapport. © 2017 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  16. Social hierarchy modulates neural responses of empathy for pain

    PubMed Central

    Feng, Chunliang; Li, Zhihao; Feng, Xue; Wang, Lili; Tian, Tengxiang

    2016-01-01

    Recent evidence indicates that empathic responses to others’ pain are modulated by various situational and individual factors. However, few studies have examined how empathy and underlying brain functions are modulated by social hierarchies, which permeate human society with an enormous impact on social behavior and cognition. In this study, social hierarchies were established based on incidental skill in a perceptual task in which all participants were mediumly ranked. Afterwards, participants were scanned with functional magnetic resonance imaging while watching inferior-status or superior-status targets receiving painful or non-painful stimulation. The results revealed that painful stimulation applied to inferior-status targets induced higher activations in the anterior insula (AI) and anterior medial cingulate cortex (aMCC), whereas these empathic brain activations were significantly attenuated in response to superior-status targets’ pain. Further, this neural empathic bias to inferior-status targets was accompanied by stronger functional couplings of AI with brain regions important in emotional processing (i.e. thalamus) and cognitive control (i.e. middle frontal gyrus). Our findings indicate that emotional sharing with others’ pain is shaped by relative positions in a social hierarchy such that underlying empathic neural responses are biased toward inferior-status compared with superior-status individuals. PMID:26516169

  17. Perceived trustworthiness shapes neural empathic responses toward others' pain.

    PubMed

    Sessa, Paola; Meconi, Federica

    2015-12-01

    As might be expected, neural empathic responses toward someone in pain are shaped by the affective/social relationship between the observer and the suffering person. Brain activity associated with empathy is sensitive to previous knowledge on the other's social conduct, such that, for instance, an unfair person in pain elicits in the observer reduced activations of empathy-related brain regions compared to a fair person. We conjectured that even in the absence of information on the personality and social behavior of an individual, empathy might be modulated by the 'first impression' based on other's physical facial features, such that the other is perceived as trustworthy or untrustworthy. By means of event-related potentials technique, we monitored in two experiments the neural empathic responses associated with the pain of trustworthy and untrustworthy faces, either computerized and parametrically manipulated (Experiment 1) and real faces (Experiment 2) in a cue-based paradigm. We observed P3 empathic reactions towards individuals looking trustworthy whereas the reactions towards individuals looking untrustworthy were negligible, if not null. An additional experiment (Experiment 3) was conducted in order to substantiate our conclusions by demonstrating that the experimental paradigm we designed did very likely activate an empathic response. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. In Search of Neural Endophenotypes of Postpartum Psychopathology and Disrupted Maternal Caregiving

    PubMed Central

    Moses-Kolko, E. L.; Horner, M. S.; Phillips, M. L.; Hipwell, A. E.; Swain, J. E.

    2015-01-01

    This is a selective review that provides the context for the study of perinatal affective disorder mechanisms and outlines directions for future research. We integrate existing literature along neural networks of interest for affective disorders and maternal caregiving: (i) the salience/fear network; (ii) the executive network; (iii) the reward/social attachment network; and (iv) the default mode network. Extant salience/fear network research reveals disparate responses and corticolimbic coupling to various stimuli based upon a predominantly depressive versus anxious (post-traumatic stress disorder) clinical phenotype. Executive network and default mode connectivity abnormalities have been described in postpartum depression (PPD), although studies are very limited in these domains. Reward/social attachment studies confirm a robust ventral striatal response to infant stimuli, including cry and happy infant faces, which is diminished in depressed, insecurely attached and substance-using mothers. The adverse parenting experiences received and the attachment insecurity of current mothers are factors that are associated with a diminution in infant stimulus-related neural activity similar to that in PPD, and raise the need for additional studies that integrate mood and attachment concepts in larger study samples. Several studies examining functional connectivity in resting state and emotional activation functional magnetic resonance imaging paradigms have revealed attenuated corticolimbic connectivity, which remains an important outcome that requires dissection with increasing precision to better define neural treatment targets. Methodological progress is expected in the coming years in terms of refining clinical phenotypes of interest and experimental paradigms, as well as enlarging samples to facilitate the examination of multiple constructs. Functional imaging promises to determine neural mechanisms underlying maternal psychopathology and impaired caregiving, such

  19. Modelling the perceptual similarity of facial expressions from image statistics and neural responses.

    PubMed

    Sormaz, Mladen; Watson, David M; Smith, William A P; Young, Andrew W; Andrews, Timothy J

    2016-04-01

    The ability to perceive facial expressions of emotion is essential for effective social communication. We investigated how the perception of facial expression emerges from the image properties that convey this important social signal, and how neural responses in face-selective brain regions might track these properties. To do this, we measured the perceptual similarity between expressions of basic emotions, and investigated how this is reflected in image measures and in the neural response of different face-selective regions. We show that the perceptual similarity of different facial expressions (fear, anger, disgust, sadness, happiness) can be predicted by both surface and feature shape information in the image. Using block design fMRI, we found that the perceptual similarity of expressions could also be predicted from the patterns of neural response in the face-selective posterior superior temporal sulcus (STS), but not in the fusiform face area (FFA). These results show that the perception of facial expression is dependent on the shape and surface properties of the image and on the activity of specific face-selective regions. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Automatic diagnosis of abnormal macula in retinal optical coherence tomography images using wavelet-based convolutional neural network features and random forests classifier

    NASA Astrophysics Data System (ADS)

    Rasti, Reza; Mehridehnavi, Alireza; Rabbani, Hossein; Hajizadeh, Fedra

    2018-03-01

    The present research intends to propose a fully automatic algorithm for the classification of three-dimensional (3-D) optical coherence tomography (OCT) scans of patients suffering from abnormal macula from normal candidates. The method proposed does not require any denoising, segmentation, retinal alignment processes to assess the intraretinal layers, as well as abnormalities or lesion structures. To classify abnormal cases from the control group, a two-stage scheme was utilized, which consists of automatic subsystems for adaptive feature learning and diagnostic scoring. In the first stage, a wavelet-based convolutional neural network (CNN) model was introduced and exploited to generate B-scan representative CNN codes in the spatial-frequency domain, and the cumulative features of 3-D volumes were extracted. In the second stage, the presence of abnormalities in 3-D OCTs was scored over the extracted features. Two different retinal SD-OCT datasets are used for evaluation of the algorithm based on the unbiased fivefold cross-validation (CV) approach. The first set constitutes 3-D OCT images of 30 normal subjects and 30 diabetic macular edema (DME) patients captured from the Topcon device. The second publicly available set consists of 45 subjects with a distribution of 15 patients in age-related macular degeneration, DME, and normal classes from the Heidelberg device. With the application of the algorithm on overall OCT volumes and 10 repetitions of the fivefold CV, the proposed scheme obtained an average precision of 99.33% on dataset1 as a two-class classification problem and 98.67% on dataset2 as a three-class classification task.

  1. Attention and emotion: does rating emotion alter neural responses to amusing and sad films?

    PubMed

    Hutcherson, C A; Goldin, P R; Ochsner, K N; Gabrieli, J D; Barrett, L Feldman; Gross, J J

    2005-09-01

    Functional neuroimaging of affective systems often includes subjective self-report of the affective response. Although self-report provides valuable information regarding participants' affective responses, prior studies have raised the concern that the attentional demands of reporting on affective experience may obscure neural activations reflecting more natural affective responses. In the present study, we used potent emotion-eliciting amusing and sad films, employed a novel method of continuous self-reported rating of emotion experience, and compared the impact of rating with passive viewing of amusing and sad films. Subjective rating of ongoing emotional responses did not decrease either self-reported experience of emotion or neural activations relative to passive viewing in any brain regions. Rating, relative to passive viewing, produced increased activity in anterior cingulate, insula, and several other areas associated with introspection of emotion. These results support the use of continuous emotion measures and emotionally engaging films to study the dynamics of emotional responding and suggest that there may be some contexts in which the attention to emotion induced by reporting emotion experience does not disrupt emotional responding either behaviorally or neurally.

  2. Behavioral and genetic correlates of the neural response to infant crying among human fathers

    PubMed Central

    Mascaro, Jennifer S.; Hackett, Patrick D.; Gouzoules, Harold; Lori, Adriana

    2014-01-01

    Although evolution has shaped human infant crying and the corresponding response from caregivers, there is marked variation in paternal involvement and caretaking behavior, highlighting the importance of understanding the neurobiology supporting optimal paternal responses to cries. We explored the neural response to infant cries in fathers of children aged 1–2, and its relationship with hormone levels, variation in the androgen receptor (AR) gene, parental attitudes and parental behavior. Although number of AR CAG trinucleotide repeats was positively correlated with neural activity in brain regions important for empathy (anterior insula and inferior frontal gyrus), restrictive attitudes were inversely correlated with neural activity in these regions and with regions involved with emotion regulation (orbitofrontal cortex). Anterior insula activity had a non-linear relationship with paternal caregiving, such that fathers with intermediate activation were most involved. These results suggest that restrictive attitudes may be associated with decreased empathy and emotion regulation in response to a child in distress, and that moderate anterior insula activity reflects an optimal level of arousal that supports engaged fathering. PMID:24336349

  3. Neural markers of errors as endophenotypes in neuropsychiatric disorders

    PubMed Central

    Manoach, Dara S.; Agam, Yigal

    2013-01-01

    Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach. PMID:23882201

  4. Neural markers of errors as endophenotypes in neuropsychiatric disorders.

    PubMed

    Manoach, Dara S; Agam, Yigal

    2013-01-01

    Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach.

  5. Maternal Neural Responses to Infant Cries and Faces: Relationships with Substance Use

    PubMed Central

    Landi, Nicole; Montoya, Jessica; Kober, Hedy; Rutherford, Helena J. V.; Mencl, W. Einar; Worhunsky, Patrick D.; Potenza, Marc N.; Mayes, Linda C.

    2011-01-01

    Substance abuse in pregnant and recently post-partum women is a major public health concern because of effects on the infant and on the ability of the adult to care for the infant. In addition to the negative health effects of teratogenic substances on fetal development, substance use can contribute to difficulties associated with the social and behavioral aspects of parenting. Neural circuits associated with parenting behavior overlap with circuits involved in addiction (e.g., frontal, striatal, and limbic systems) and thus may be co-opted for the craving/reward cycle associated with substance use and abuse and be less available for parenting. The current study investigates the degree to which neural circuits associated with parenting are disrupted in mothers who are substance-using. Specifically, we used functional magnetic resonance imaging to examine the neural response to emotional infant cues (faces and cries) in substance-using compared to non-using mothers. In response to both faces (of varying emotional valence) and cries (of varying distress levels), substance-using mothers evidenced reduced neural activation in regions that have been previously implicated in reward and motivation as well as regions involved in cognitive control. Specifically, in response to faces, substance users showed reduced activation in prefrontal regions, including the dorsolateral and ventromedial prefrontal cortices, as well as visual processing (occipital lobes) and limbic regions (parahippocampus and amygdala). Similarly, in response to infant cries, substance-using mothers showed reduced activation relative to non-using mothers in prefrontal regions, auditory sensory processing regions, insula and limbic regions (parahippocampus and amygdala). These findings suggest that infant stimuli may be less salient for substance-using mothers, and such reduced saliency may impair developing infant-caregiver attachment and the ability of mothers to respond appropriately to their infants

  6. Divergent neural responses to narrative speech in disorders of consciousness.

    PubMed

    Iotzov, Ivan; Fidali, Brian C; Petroni, Agustin; Conte, Mary M; Schiff, Nicholas D; Parra, Lucas C

    2017-11-01

    Clinical assessment of auditory attention in patients with disorders of consciousness is often limited by motor impairment. Here, we employ intersubject correlations among electroencephalography responses to naturalistic speech in order to assay auditory attention among patients and healthy controls. Electroencephalographic data were recorded from 20 subjects with disorders of consciousness and 14 healthy controls during of two narrative audio stimuli, presented both forwards and time-reversed. Intersubject correlation of evoked electroencephalography signals were calculated, comparing responses of both groups to those of the healthy control subjects. This analysis was performed blinded and subsequently compared to the diagnostic status of each patient based on the Coma Recovery Scale-Revised. Subjects with disorders of consciousness exhibit significantly lower intersubject correlation than healthy controls during narrative speech. Additionally, while healthy subjects had higher intersubject correlation values in forwards versus backwards presentation, neural responses did not vary significantly with the direction of playback in subjects with disorders of consciousness. Increased intersubject correlation values in the backward speech condition were noted with improving disorder of consciousness diagnosis, both in cross-sectional analysis and in a subset of patients with longitudinal data. Intersubject correlation of neural responses to narrative speech audition differentiates healthy controls from patients and appears to index clinical diagnoses in disorders of consciousness.

  7. Genetic influences on phase synchrony of brain oscillations supporting response inhibition.

    PubMed

    Müller, Viktor; Anokhin, Andrey P; Lindenberger, Ulman

    2017-05-01

    Phase synchronization of neuronal oscillations is a fundamental mechanism underlying cognitive processing and behavior, including context-dependent response production and inhibition. Abnormalities in neural synchrony can lead to abnormal information processing and contribute to cognitive and behavioral deficits in neuropsychiatric disorders. However, little is known about genetic and environmental contributions to individual differences in cortical oscillatory dynamics underlying response inhibition. This study examined heritability of event-related phase synchronization of brain oscillations in 302 young female twins including 94 MZ and 57 DZ pairs performing a cued Go/No-Go version of the Continuous Performance Test (CPT). We used the Phase Locking Index (PLI) to assess inter-trial phase clustering (synchrony) in several frequency bands in two time intervals after stimulus onset (0-300 and 301-600ms). Response inhibition (i.e., successful response suppression in No-Go trials) was characterized by a transient increase in phase synchronization of delta- and theta-band oscillations in the fronto-central midline region. Genetic analysis showed significant heritability of the phase locking measures related to response inhibition, with 30 to 49% of inter-individual variability being accounted for by genetic factors. This is the first study providing evidence for heritability of task-related neural synchrony. The present results suggest that PLI can serve as an indicator of genetically transmitted individual differences in neural substrates of response inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Distinguishing Adolescents With ADHD From Their Unaffected Siblings and Healthy Comparison Subjects by Neural Activation Patterns During Response Inhibition.

    PubMed

    van Rooij, Daan; Hoekstra, Pieter J; Mennes, Maarten; von Rhein, Daniel; Thissen, Andrieke J A M; Heslenfeld, Dirk; Zwiers, Marcel P; Faraone, Stephen V; Oosterlaan, Jaap; Franke, Barbara; Rommelse, Nanda; Buitelaar, Jan K; Hartman, Catharina A

    2015-07-01

    Dysfunctional response inhibition is a key executive function impairment in attention deficit hyperactivity disorder (ADHD). Still, behavioral response inhibition measures do not consistently differentiate affected from unaffected individuals. The authors therefore investigated neural correlates of response inhibition and the familial nature of these neural correlates. Functional MRI measurements of neural activation during the stop-signal task and behavioral measures of response inhibition were obtained in adolescents and young adults with ADHD (N=185), their unaffected siblings (N=111), and healthy comparison subjects (N=124). Stop-signal task reaction times were longer and error rates were higher in participants with ADHD, but not in their unaffected siblings, while reaction time variability was higher in both groups than in comparison subjects. Relative to comparison subjects, participants with ADHD and unaffected siblings had neural hypoactivation in frontal-striatal and frontal-parietal networks, whereby activation in inferior frontal and temporal/parietal nodes in unaffected siblings was intermediate between levels of participants with ADHD and comparison subjects. Furthermore, neural activation in inferior frontal nodes correlated with stop-signal reaction times, and activation in both inferior frontal and temporal/parietal nodes correlated with ADHD severity. Neural activation alterations in ADHD are more robust than behavioral response inhibition deficits and explain variance in response inhibition and ADHD severity. Although only affected participants with ADHD have deficient response inhibition, hypoactivation in inferior frontal and temporal-parietal nodes in unaffected siblings supports the familial nature of the underlying neural process. Activation deficits in these nodes may be useful as endophenotypes that extend beyond the affected individuals in the family.

  9. Learning quadratic receptive fields from neural responses to natural stimuli.

    PubMed

    Rajan, Kanaka; Marre, Olivier; Tkačik, Gašper

    2013-07-01

    Models of neural responses to stimuli with complex spatiotemporal correlation structure often assume that neurons are selective for only a small number of linear projections of a potentially high-dimensional input. In this review, we explore recent modeling approaches where the neural response depends on the quadratic form of the input rather than on its linear projection, that is, the neuron is sensitive to the local covariance structure of the signal preceding the spike. To infer this quadratic dependence in the presence of arbitrary (e.g., naturalistic) stimulus distribution, we review several inference methods, focusing in particular on two information theory-based approaches (maximization of stimulus energy and of noise entropy) and two likelihood-based approaches (Bayesian spike-triggered covariance and extensions of generalized linear models). We analyze the formal relationship between the likelihood-based and information-based approaches to demonstrate how they lead to consistent inference. We demonstrate the practical feasibility of these procedures by using model neurons responding to a flickering variance stimulus.

  10. Neural networks distinguish between taste qualities based on receptor cell population responses.

    PubMed

    Varkevisser, B; Peterson, D; Ogura, T; Kinnamon, S C

    2001-06-01

    Response features of taste receptor cell action potentials were examined using an artificial neural network to determine whether they contain information about taste quality. Using the loose patch technique to record from hamster taste buds in vivo we recorded population responses of single fungiform papillae to NaCl (100 mM), sucrose (200 mM) and the synthetic sweetener NC-00274-01 (NC-01) (200 microM). Features of each response describing both burst and inter-burst characteristics were then presented to an artificial neural network for pairwise classification of taste stimuli. Responses to NaCl could be distinguished from those to both NC-01 and sucrose with accuracies of up to 86%. In contrast, pairwise comparisons between sucrose and NC-01 were not successful, scoring at chance (50%). Also, comparisons between two different concentrations of NaCl, 0.01 and 0.005 M, scored at chance. Pairwise comparisons using only those features that relate to the inter-burst behavior of the response (i.e. bursting rate) did not hinder the performance of the neural network as both sweeteners versus NaCl received scores of 75--85%. Comparisons using features corresponding to each individual burst scored poorly, receiving scores only slightly above chance. We then compared the sweeteners with varying concentrations of NaCl (0.1, 0.01, 0.005 and 0.001 M) using only those features corresponding to bursting rate within a 1 s time window. The neural network was capable of distinguishing between NaCl and NC-01 at all concentrations tested; while comparisons between NaCl and sucrose received high scores at all concentrations except 0.001 M. These results show that two different taste qualities can be distinguished from each other based solely on the bursting rates of action potentials in single taste buds and that this distinction is independent of stimulation intensity down to 0.001 M NaCl. These data suggest that action potentials in taste receptor cells may play a role in taste

  11. Differential neural responses to child and sexual stimuli in human fathers and non-fathers and their hormonal correlates

    PubMed Central

    Mascaro, Jennifer S.; Hackett, Patrick D.; Rilling, James K.

    2015-01-01

    Despite the well-documented importance of paternal caregiving for positive child development, little is known about the neural changes that accompany the transition to fatherhood in humans, or about how changes in hormone levels affect paternal brain function. We compared fathers of children aged 1–2 with non-fathers in terms of hormone levels (oxytocin and testosterone), neural responses to child picture stimuli, and neural responses to visual sexual stimuli. Compared to non-fathers, fathers had significantly higher levels of plasma oxytocin and lower levels of plasma testosterone. In response to child picture stimuli, fathers showed stronger activation than non-fathers within regions important for face emotion processing (caudal middle frontal gyrus [MFG]), mentalizing (temporo-parietal junction [TPJ]) and reward processing (medial orbitofrontal cortex [mOFC]). On the other hand, non-fathers had significantly stronger neural responses to sexually provocative images in regions important for reward and approach-related motivation (dorsal caudate and nucleus accumbens). Testosterone levels were negatively correlated with responses to child stimuli in the MFG. Surprisingly, neither testosterone nor oxytocin levels predicted neural responses to sexual stimuli. Our results suggest that the decline in testosterone that accompanies the transition to fatherhood may be important for augmenting empathy toward children. PMID:24882167

  12. Transient and sustained neural responses to death-related linguistic cues

    PubMed Central

    Shi, Zhenhao

    2013-01-01

    Recent research showed that perception of death-related vs death-unrelated linguistic cues produced increased frontoparietal activity but decreased insular activity. This study investigated (i) whether the increased frontoparietal and decreased insular activities are, respectively, associated with transient trial-specific processes of death-related linguistic cues and sustained death-related thought during death-relevance judgments on linguistic cues and (ii) whether the neural activity underlying death-related thought can predict individuals’ dispositional death anxiety. Participants were presented with death-related/unrelated words, life-related/unrelated words, and negative-valence/neutral words in separate sessions. Participants were scanned using functional magnetic resonance imaging while performing death-relevance, life-relevance, and valence judgments on the words, respectively. The contrast of death-related vs death-unrelated words during death-relevance judgments revealed transient increased activity in the left inferior parietal lobule, the right frontal eye field, and the right superior parietal lobule. The contrast of death-relevance judgments vs life-relevance/valence judgments showed decreased activity in the bilateral insula. The sustained insular activity was correlated with dispositional death anxiety, but only in those with weak transient frontoparietal responses to death-related words. Our results dissociate the transient and sustained neural responses to death-related linguistic cues and suggest that the combination of the transient and sustained neural activities can predict dispositional death anxiety. PMID:22422804

  13. Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis.

    PubMed

    Carucci, Nicoletta; Cacci, Emanuele; Nisi, Paola S; Licursi, Valerio; Paul, Yu-Lee; Biagioni, Stefano; Negri, Rodolfo; Rugg-Gunn, Peter J; Lupo, Giuseppe

    2017-04-01

    During vertebrate neural development, positional information is largely specified by extracellular morphogens. Their distribution, however, is very dynamic due to the multiple roles played by the same signals in the developing and adult neural tissue. This suggests that neural progenitors are able to modify their competence to respond to morphogen signalling and autonomously maintain positional identities after their initial specification. In this work, we take advantage of in vitro culture systems of mouse neural stem/progenitor cells (NSPCs) to show that NSPCs isolated from rostral or caudal regions of the mouse neural tube are differentially responsive to retinoic acid (RA), a pivotal morphogen for the specification of posterior neural fates. Hoxb genes are among the best known RA direct targets in the neural tissue, yet we found that RA could promote their transcription only in caudal but not in rostral NSPCs. Correlating with these effects, key RA-responsive regulatory regions in the Hoxb cluster displayed opposite enrichment of activating or repressing histone marks in rostral and caudal NSPCs. Finally, RA was able to strengthen Hoxb chromatin activation in caudal NSPCs, but was ineffective on the repressed Hoxb chromatin of rostral NSPCs. These results suggest that the response of NSPCs to morphogen signalling across the rostrocaudal axis of the neural tube may be gated by the epigenetic configuration of target patterning genes, allowing long-term maintenance of intrinsic positional values in spite of continuously changing extrinsic signals.

  14. Response Monitoring, Repetitive Behaviour and Anterior Cingulate Abnormalities in Autism Spectrum Disorders (ASD)

    ERIC Educational Resources Information Center

    Thakkar, Katharine N.; Polli, Frida E.; Joseph, Robert M.; Tuch, David S.; Hadjikhani, Nouchine; Barton, Jason J. S.; Manoach, Dara S.

    2008-01-01

    Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Response monitoring involves evaluating the consequences of behaviour and making adjustments to optimize outcomes. Deficiencies in this function, and abnormalities in the anterior cingulate cortex (ACC) on which it relies, have been reported as contributing…

  15. Effects of Acute Alcohol Intoxication on Empathic Neural Responses for Pain

    PubMed Central

    Hu, Yang; Cui, Zhuoya; Fan, Mingxia; Pei, Yilai; Wang, Zhaoxin

    2018-01-01

    The questions whether and how empathy for pain can be modulated by acute alcohol intoxication in the non-dependent population remain unanswered. To address these questions, a double-blind, placebo-controlled, within-subject study design was adopted in this study, in which healthy social drinkers were asked to complete a pain-judgment task using pictures depicting others' body parts in painful or non-painful situations during fMRI scanning, either under the influence of alcohol intoxication or placebo conditions. Empathic neural activity for pain was reduced by alcohol intoxication only in the dorsal anterior cingulate cortex (dACC). More interestingly, we observed that empathic neural activity for pain in the right anterior insula (rAI) was significantly correlated with trait empathy only after alcohol intoxication, along with impaired functional connectivity between the rAI and the fronto-parietal attention network. Our results reveal that alcohol intoxication not only inhibits empathic neural responses for pain but also leads to trait empathy inflation, possibly via impaired top-down attentional control. These findings help to explain the neural mechanism underlying alcohol-related social problems. PMID:29354044

  16. Effects of Acute Alcohol Intoxication on Empathic Neural Responses for Pain.

    PubMed

    Hu, Yang; Cui, Zhuoya; Fan, Mingxia; Pei, Yilai; Wang, Zhaoxin

    2017-01-01

    The questions whether and how empathy for pain can be modulated by acute alcohol intoxication in the non-dependent population remain unanswered. To address these questions, a double-blind, placebo-controlled, within-subject study design was adopted in this study, in which healthy social drinkers were asked to complete a pain-judgment task using pictures depicting others' body parts in painful or non-painful situations during fMRI scanning, either under the influence of alcohol intoxication or placebo conditions. Empathic neural activity for pain was reduced by alcohol intoxication only in the dorsal anterior cingulate cortex (dACC). More interestingly, we observed that empathic neural activity for pain in the right anterior insula (rAI) was significantly correlated with trait empathy only after alcohol intoxication, along with impaired functional connectivity between the rAI and the fronto-parietal attention network. Our results reveal that alcohol intoxication not only inhibits empathic neural responses for pain but also leads to trait empathy inflation, possibly via impaired top-down attentional control. These findings help to explain the neural mechanism underlying alcohol-related social problems.

  17. Maladaptive Neural Synchrony in Tinnitus: Origin and Restoration

    PubMed Central

    Eggermont, Jos J.; Tass, Peter A.

    2015-01-01

    Tinnitus is the conscious perception of sound heard in the absence of physical sound sources external or internal to the body, reflected in aberrant neural synchrony of spontaneous or resting-state brain activity. Neural synchrony is generated by the nearly simultaneous firing of individual neurons, of the synchronization of membrane-potential changes in local neural groups as reflected in the local field potentials, resulting in the presence of oscillatory brain waves in the EEG. Noise-induced hearing loss, often resulting in tinnitus, causes a reorganization of the tonotopic map in auditory cortex and increased spontaneous firing rates and neural synchrony. Spontaneous brain rhythms rely on neural synchrony. Abnormal neural synchrony in tinnitus appears to be confined to specific frequency bands of brain rhythms. Increases in delta-band activity are generated by deafferented/deprived neuronal networks resulting from hearing loss. Coordinated reset (CR) stimulation was developed in order to specifically counteract such abnormal neuronal synchrony by desynchronization. The goal of acoustic CR neuromodulation is to desynchronize tinnitus-related abnormal delta-band oscillations. CR neuromodulation does not require permanent stimulus delivery in order to achieve long-lasting desynchronization or even a full-blown anti-kindling but may have cumulative effects, i.e., the effect of different CR epochs separated by pauses may accumulate. Unlike other approaches, acoustic CR neuromodulation does not intend to reduce tinnitus-related neuronal activity by employing lateral inhibition. The potential efficacy of acoustic CR modulation was shown in a clinical proof of concept trial, where effects achieved in 12 weeks of treatment delivered 4–6 h/day persisted through a preplanned 4-week therapy pause and showed sustained long-term effects after 10 months of therapy, leading to 75% responders. PMID:25741316

  18. Temporal abnormalities in children with developmental dyscalculia.

    PubMed

    Vicario, Carmelo Mario; Rappo, Gaetano; Pepi, Annamaria; Pavan, Andrea; Martino, Davide

    2012-01-01

    Recent imaging studies have associated Developmental dyscalculia (DD) to structural and functional alterations corresponding Parietal and the Prefrontal cortex (PFC). Since these areas were shown also to be involved in timing abilities, we hypothesized that time processing is abnormal in DD. We compared time processing abilities between 10 children with pure DD (8 years old) and 11 age-matched healthy children. Results show that the DD group underestimated duration of a sub-second scale when asked to perform a time comparison task. The timing abnormality observed in our DD participants is consistent with evidence of a shared fronto-parietal neural network for representing time and quantity.

  19. Eye Movement Abnormalities in Joubert Syndrome

    PubMed Central

    Weiss, Avery H.; Doherty, Dan; Parisi, Melissa; Shaw, Dennis; Glass, Ian; Phillips, James O.

    2011-01-01

    Purpose Joubert syndrome is a genetic disorder characterized by hypoplasia of the midline cerebellum and deficiency of crossed connections between neural structures in the brain stem that control eye movements. The goal of the study was to quantify the eye movement abnormalities that occur in Joubert syndrome. Methods Eye movements were recorded in response to stationary stimuli and stimuli designed to elicit smooth pursuit, saccades, optokinetic nystagmus (OKN), vestibulo-ocular reflex (VOR), and vergence using video-oculography or Skalar search coils in 8 patients with Joubert syndrome. All patients underwent high-resolution magnetic resonance imaging (MRI). Results All patients had the highly characteristic molar tooth sign on brain MRI. Six patients had conjugate pendular (n = 4) or see-saw nystagmus (n = 2); gaze holding was stable in four patients. Smooth-pursuit gains were 0.28 to 1.19, 0.11 to 0.68, and 0.33 to 0.73 at peak stimulus velocities of 10, 20, and 30 deg/s in six patients; smooth pursuit could not be elicited in four patients. Saccade gains in five patients ranged from 0.35 to 0.91 and velocities ranged from 60.9 to 259.5 deg/s. Targeted saccades could not be elicited in five patients. Horizontal OKN gain was uniformly reduced across gratings drifted at velocities of 15, 30, and 45 deg/s. VOR gain was 0.8 or higher and phase appropriate in three of seven subjects; VOR gain was 0.3 or less and phase was indeterminate in four subjects. Conclusions The abnormalities in gaze-holding and eye movements are consistent with the distributed abnormalities of midline cerebellum and brain stem regions associated with Joubert syndrome. PMID:19443711

  20. Social hierarchy modulates neural responses of empathy for pain.

    PubMed

    Feng, Chunliang; Li, Zhihao; Feng, Xue; Wang, Lili; Tian, Tengxiang; Luo, Yue-Jia

    2016-03-01

    Recent evidence indicates that empathic responses to others' pain are modulated by various situational and individual factors. However, few studies have examined how empathy and underlying brain functions are modulated by social hierarchies, which permeate human society with an enormous impact on social behavior and cognition. In this study, social hierarchies were established based on incidental skill in a perceptual task in which all participants were mediumly ranked. Afterwards, participants were scanned with functional magnetic resonance imaging while watching inferior-status or superior-status targets receiving painful or non-painful stimulation. The results revealed that painful stimulation applied to inferior-status targets induced higher activations in the anterior insula (AI) and anterior medial cingulate cortex (aMCC), whereas these empathic brain activations were significantly attenuated in response to superior-status targets' pain. Further, this neural empathic bias to inferior-status targets was accompanied by stronger functional couplings of AI with brain regions important in emotional processing (i.e. thalamus) and cognitive control (i.e. middle frontal gyrus). Our findings indicate that emotional sharing with others' pain is shaped by relative positions in a social hierarchy such that underlying empathic neural responses are biased toward inferior-status compared with superior-status individuals. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  1. Electrosensory neural responses to natural electro-communication stimuli are distributed along a continuum

    PubMed Central

    Sproule, Michael K. J.

    2017-01-01

    Neural heterogeneities are seen ubiquitously within the brain and greatly complicate classification efforts. Here we tested whether the responses of an anatomically well-characterized sensory neuron population to natural stimuli could be used for functional classification. To do so, we recorded from pyramidal cells within the electrosensory lateral line lobe (ELL) of the weakly electric fish Apteronotus leptorhynchus in response to natural electro-communication stimuli as these cells can be anatomically classified into six different types. We then used two independent methodologies to functionally classify responses: one relies of reducing the dimensionality of a feature space while the other directly compares the responses themselves. Both methodologies gave rise to qualitatively similar results: while ON and OFF-type cells could easily be distinguished from one another, ELL pyramidal neuron responses are actually distributed along a continuum rather than forming distinct clusters due to heterogeneities. We discuss the implications of our results for neural coding and highlight some potential advantages. PMID:28384244

  2. Spatially Pooled Contrast Responses Predict Neural and Perceptual Similarity of Naturalistic Image Categories

    PubMed Central

    Groen, Iris I. A.; Ghebreab, Sennay; Lamme, Victor A. F.; Scholte, H. Steven

    2012-01-01

    The visual world is complex and continuously changing. Yet, our brain transforms patterns of light falling on our retina into a coherent percept within a few hundred milliseconds. Possibly, low-level neural responses already carry substantial information to facilitate rapid characterization of the visual input. Here, we computationally estimated low-level contrast responses to computer-generated naturalistic images, and tested whether spatial pooling of these responses could predict image similarity at the neural and behavioral level. Using EEG, we show that statistics derived from pooled responses explain a large amount of variance between single-image evoked potentials (ERPs) in individual subjects. Dissimilarity analysis on multi-electrode ERPs demonstrated that large differences between images in pooled response statistics are predictive of more dissimilar patterns of evoked activity, whereas images with little difference in statistics give rise to highly similar evoked activity patterns. In a separate behavioral experiment, images with large differences in statistics were judged as different categories, whereas images with little differences were confused. These findings suggest that statistics derived from low-level contrast responses can be extracted in early visual processing and can be relevant for rapid judgment of visual similarity. We compared our results with two other, well- known contrast statistics: Fourier power spectra and higher-order properties of contrast distributions (skewness and kurtosis). Interestingly, whereas these statistics allow for accurate image categorization, they do not predict ERP response patterns or behavioral categorization confusions. These converging computational, neural and behavioral results suggest that statistics of pooled contrast responses contain information that corresponds with perceived visual similarity in a rapid, low-level categorization task. PMID:23093921

  3. Behavioral and genetic correlates of the neural response to infant crying among human fathers.

    PubMed

    Mascaro, Jennifer S; Hackett, Patrick D; Gouzoules, Harold; Lori, Adriana; Rilling, James K

    2014-11-01

    Although evolution has shaped human infant crying and the corresponding response from caregivers, there is marked variation in paternal involvement and caretaking behavior, highlighting the importance of understanding the neurobiology supporting optimal paternal responses to cries. We explored the neural response to infant cries in fathers of children aged 1-2, and its relationship with hormone levels, variation in the androgen receptor (AR) gene, parental attitudes and parental behavior. Although number of AR CAG trinucleotide repeats was positively correlated with neural activity in brain regions important for empathy (anterior insula and inferior frontal gyrus), restrictive attitudes were inversely correlated with neural activity in these regions and with regions involved with emotion regulation (orbitofrontal cortex). Anterior insula activity had a non-linear relationship with paternal caregiving, such that fathers with intermediate activation were most involved. These results suggest that restrictive attitudes may be associated with decreased empathy and emotion regulation in response to a child in distress, and that moderate anterior insula activity reflects an optimal level of arousal that supports engaged fathering. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  4. Selective Roles of Normal and Mutant Huntingtin in Neural Induction and Early Neurogenesis

    PubMed Central

    Nguyen, Giang D.; Gokhan, Solen; Molero, Aldrin E.; Mehler, Mark F.

    2013-01-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by abnormal polyglutamine expansion in the amino-terminal end of the huntingtin protein (Htt) and characterized by progressive striatal and cortical pathology. Previous reports have shown that Htt is essential for embryogenesis, and a recent study by our group revealed that the pathogenic form of Htt (mHtt) causes impairments in multiple stages of striatal development. In this study, we have examined whether HD-associated striatal developmental deficits are reflective of earlier maturational alterations occurring at the time of neurulation by assessing differential roles of Htt and mHtt during neural induction and early neurogenesis using an in vitro mouse embryonic stem cell (ESC) clonal assay system. We demonstrated that the loss of Htt in ESCs (KO ESCs) severely disrupts the specification of primitive and definitive neural stem cells (pNSCs, dNSCs, respectively) during the process of neural induction. In addition, clonally derived KO pNSCs and dNSCs displayed impaired proliferative potential, enhanced cell death and altered multi-lineage potential. Conversely, as observed in HD knock-in ESCs (Q111 ESCs), mHtt enhanced the number and size of pNSC clones, which exhibited enhanced proliferative potential and precocious neuronal differentiation. The transition from Q111 pNSCs to fibroblast growth factor 2 (FGF2)-responsive dNSCs was marked by potentiation in the number of dNSCs and altered proliferative potential. The multi-lineage potential of Q111 dNSCs was also enhanced with precocious neurogenesis and oligodendrocyte progenitor elaboration. The generation of Q111 epidermal growth factor (EGF)-responsive dNSCs was also compromised, whereas their multi-lineage potential was unaltered. These abnormalities in neural induction were associated with differential alterations in the expression profiles of Notch, Hes1 and Hes5. These cumulative observations indicate that Htt is required for multiple stages

  5. Automatic diagnosis of abnormal macula in retinal optical coherence tomography images using wavelet-based convolutional neural network features and random forests classifier.

    PubMed

    Rasti, Reza; Mehridehnavi, Alireza; Rabbani, Hossein; Hajizadeh, Fedra

    2018-03-01

    The present research intends to propose a fully automatic algorithm for the classification of three-dimensional (3-D) optical coherence tomography (OCT) scans of patients suffering from abnormal macula from normal candidates. The method proposed does not require any denoising, segmentation, retinal alignment processes to assess the intraretinal layers, as well as abnormalities or lesion structures. To classify abnormal cases from the control group, a two-stage scheme was utilized, which consists of automatic subsystems for adaptive feature learning and diagnostic scoring. In the first stage, a wavelet-based convolutional neural network (CNN) model was introduced and exploited to generate B-scan representative CNN codes in the spatial-frequency domain, and the cumulative features of 3-D volumes were extracted. In the second stage, the presence of abnormalities in 3-D OCTs was scored over the extracted features. Two different retinal SD-OCT datasets are used for evaluation of the algorithm based on the unbiased fivefold cross-validation (CV) approach. The first set constitutes 3-D OCT images of 30 normal subjects and 30 diabetic macular edema (DME) patients captured from the Topcon device. The second publicly available set consists of 45 subjects with a distribution of 15 patients in age-related macular degeneration, DME, and normal classes from the Heidelberg device. With the application of the algorithm on overall OCT volumes and 10 repetitions of the fivefold CV, the proposed scheme obtained an average precision of 99.33% on dataset1 as a two-class classification problem and 98.67% on dataset2 as a three-class classification task. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  6. Connectomics and graph theory analyses: Novel insights into network abnormalities in epilepsy.

    PubMed

    Gleichgerrcht, Ezequiel; Kocher, Madison; Bonilha, Leonardo

    2015-11-01

    The assessment of neural networks in epilepsy has become increasingly relevant in the context of translational research, given that localized forms of epilepsy are more likely to be related to abnormal function within specific brain networks, as opposed to isolated focal brain pathology. It is notable that variability in clinical outcomes from epilepsy treatment may be a reflection of individual patterns of network abnormalities. As such, network endophenotypes may be important biomarkers for the diagnosis and treatment of epilepsy. Despite its exceptional potential, measuring abnormal networks in translational research has been thus far constrained by methodologic limitations. Fortunately, recent advancements in neuroscience, particularly in the field of connectomics, permit a detailed assessment of network organization, dynamics, and function at an individual level. Data from the personal connectome can be assessed using principled forms of network analyses based on graph theory, which may disclose patterns of organization that are prone to abnormal dynamics and epileptogenesis. Although the field of connectomics is relatively new, there is already a rapidly growing body of evidence to suggest that it can elucidate several important and fundamental aspects of abnormal networks to epilepsy. In this article, we provide a review of the emerging evidence from connectomics research regarding neural network architecture, dynamics, and function related to epilepsy. We discuss how connectomics may bring together pathophysiologic hypotheses from conceptual and basic models of epilepsy and in vivo biomarkers for clinical translational research. By providing neural network information unique to each individual, the field of connectomics may help to elucidate variability in clinical outcomes and open opportunities for personalized medicine approaches to epilepsy. Connectomics involves complex and rich data from each subject, thus collaborative efforts to enable the

  7. Common and Distinct Neural Mechanisms of Attentional Switching and Response Conflict

    PubMed Central

    Kim, Chobok; Johnson, Nathan F.; Gold, Brian T.

    2012-01-01

    The human capacities for overcoming prepotent actions and flexibly switching between tasks represent cornerstones of cognitive control. Functional neuroimaging has implicated a diverse set of brain regions contributing to each of these cognitive control processes. However, the extent to which attentional switching and response conflict draw on shared or distinct neural mechanisms remains unclear. The current study examined the neural correlates of response conflict and attentional switching using event-related functional magnetic resonance imaging (fMRI) and a fully randomized 2×2 design. We manipulated an arrow-word version of the Stroop task to measure conflict and switching in the context of a single task decision, in response to a common set of stimuli. Under these common conditions, both behavioral and imaging data showed significant main effects of conflict and switching but no interaction. However, conjunction analyses identified frontal regions involved in both switching and response conflict, including the dorsal anterior cingulate cortex (dACC) and left inferior frontal junction. In addition, connectivity analyses demonstrated task-dependent functional connectivity patterns between dACC and inferior temporal cortex for attentional switching and between dACC and posterior parietal cortex for response conflict. These results suggest that the brain makes use of shared frontal regions, but can dynamically modulate the connectivity patterns of some of those regions, to deal with attentional switching and response conflict. PMID:22750124

  8. Biomaterials and computation: a strategic alliance to investigate emergent responses of neural cells.

    PubMed

    Sergi, Pier Nicola; Cavalcanti-Adam, Elisabetta Ada

    2017-03-28

    Topographical and chemical cues drive migration, outgrowth and regeneration of neurons in different and crucial biological conditions. In the natural extracellular matrix, their influences are so closely coupled that they result in complex cellular responses. As a consequence, engineered biomaterials are widely used to simplify in vitro conditions, disentangling intricate in vivo behaviours, and narrowing the investigation on particular emergent responses. Nevertheless, how topographical and chemical cues affect the emergent response of neural cells is still unclear, thus in silico models are used as additional tools to reproduce and investigate the interactions between cells and engineered biomaterials. This work aims at presenting the synergistic use of biomaterials-based experiments and computation as a strategic way to promote the discovering of complex neural responses as well as to allow the interactions between cells and biomaterials to be quantitatively investigated, fostering a rational design of experiments.

  9. Neural responses to taxation and voluntary giving reveal motives for charitable donations.

    PubMed

    Harbaugh, William T; Mayr, Ulrich; Burghart, Daniel R

    2007-06-15

    Civil societies function because people pay taxes and make charitable contributions to provide public goods. One possible motive for charitable contributions, called "pure altruism," is satisfied by increases in the public good no matter the source or intent. Another possible motive, "warm glow," is only fulfilled by an individual's own voluntary donations. Consistent with pure altruism, we find that even mandatory, tax-like transfers to a charity elicit neural activity in areas linked to reward processing. Moreover, neural responses to the charity's financial gains predict voluntary giving. However, consistent with warm glow, neural activity further increases when people make transfers voluntarily. Both pure altruism and warm-glow motives appear to determine the hedonic consequences of financial transfers to the public good.

  10. Familial Risk for Insomnia Is Associated With Abnormal Cortisol Response to Stress.

    PubMed

    Drake, Christopher L; Cheng, Philip; Almeida, David M; Roth, Thomas

    2017-10-01

    Abnormalities in the stress system have been implicated in insomnia. However, studies examining physiological stress regulation in insomnia have not consistently detected differences in the hypothalamic-pituitary-adrenal (HPA)-axis response to stress. One explanation may be that deficits in the stress system are associated specifically with a biological vulnerability to insomnia rather than the phenotypic expression of insomnia. To examine stress response as a function of vulnerability to insomnia, this study tested response to the Trier Social Stress Test in a sample of healthy sleepers with varying familial risks for insomnia. Thirty-five healthy individuals with and without familial risk for insomnia were recruited to complete a laboratory stressor. Participants with one or both biological parents with insomnia were categorized as positive for familial risk, whereas those without biological parents with insomnia were categorized as negative for familial risk. Participants completed the Trier Social Stress Test in the laboratory, and psychological and physiological (autonomic and HPA-axis) responses were compared. Despite self-reported increases in anxiety, those positive for familial risk exhibited a blunted cortisol response relative to those without familial risk for insomnia. Individuals with blunted cortisol also reported heightened reactivity to personal life stressors, including increased sleep disturbances, elevated cognitive intrusions, and more behavioral avoidance. Findings from this study provide initial evidence that abnormal stress regulation may be a biological predisposing factor conferred via familial risk for insomnia. This deficit may also predict negative consequences over time, including insomnia and the associated psychiatric comorbidities. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  11. Body mass is positively associated with neural response to sweet taste, but not alcohol, among drinkers.

    PubMed

    Gardiner, Casey K; YorkWilliams, Sophie L; Bryan, Angela D; Hutchison, Kent E

    2017-07-28

    Obesity is a large and growing public health concern, presenting enormous economic and health costs to individuals and society. A burgeoning literature demonstrates that overweight and obese individuals display different neural processing of rewarding stimuli, including caloric substances, as compared to healthy weight individuals. However, much extant research on the neurobiology of obesity has focused on addiction models, without highlighting potentially separable neural underpinnings of caloric intake versus substance use. The present research explores these differences by examining neural response to alcoholic beverages and a sweet non-alcoholic beverage, among a sample of individuals with varying weight status and patterns of alcohol use and misuse. Participants received tastes of a sweet beverage (litchi juice) and alcoholic beverages during fMRI scanning. When controlling for alcohol use, elevated weight status was associated with increased activation in response to sweet taste in regions including the cingulate cortex, hippocampus, precuneus, and fusiform gyrus. However, weight status was not associated with neural response to alcoholic beverages. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice.

    PubMed

    Arime, Yosefu; Akiyama, Kazufumi

    2017-01-01

    Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC) and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP) mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days) of either saline or PCP (10 mg/kg): (1) a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2) brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s) in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2-3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells) in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2-3 of the prelimbic cortex of the PFC.

  13. Abnormal neural activation patterns underlying working memory impairment in chronic phencyclidine-treated mice

    PubMed Central

    Akiyama, Kazufumi

    2017-01-01

    Working memory impairment is a hallmark feature of schizophrenia and is thought be caused by dysfunctions in the prefrontal cortex (PFC) and associated brain regions. However, the neural circuit anomalies underlying this impairment are poorly understood. The aim of this study is to assess working memory performance in the chronic phencyclidine (PCP) mouse model of schizophrenia, and to identify the neural substrates of working memory. To address this issue, we conducted the following experiments for mice after withdrawal from chronic administration (14 days) of either saline or PCP (10 mg/kg): (1) a discrete paired-trial variable-delay task in T-maze to assess working memory, and (2) brain-wide c-Fos mapping to identify activated brain regions relevant to this task performance either 90 min or 0 min after the completion of the task, with each time point examined under working memory effort and basal conditions. Correct responses in the test phase of the task were significantly reduced across delays (5, 15, and 30 s) in chronic PCP-treated mice compared with chronic saline-treated controls, suggesting delay-independent impairments in working memory in the PCP group. In layer 2–3 of the prelimbic cortex, the number of working memory effort-elicited c-Fos+ cells was significantly higher in the chronic PCP group than in the chronic saline group. The main effect of working memory effort relative to basal conditions was to induce significantly increased c-Fos+ cells in the other layers of prelimbic cortex and the anterior cingulate and infralimbic cortex regardless of the different chronic regimens. Conversely, this working memory effort had a negative effect (fewer c-Fos+ cells) in the ventral hippocampus. These results shed light on some putative neural networks relevant to working memory impairments in mice chronically treated with PCP, and emphasize the importance of the layer 2–3 of the prelimbic cortex of the PFC. PMID:29253020

  14. Neural Responses to Heartbeats in the Default Network Encode the Self in Spontaneous Thoughts.

    PubMed

    Babo-Rebelo, Mariana; Richter, Craig G; Tallon-Baudry, Catherine

    2016-07-27

    The default network (DN) has been consistently associated with self-related cognition, but also to bodily state monitoring and autonomic regulation. We hypothesized that these two seemingly disparate functional roles of the DN are functionally coupled, in line with theories proposing that selfhood is grounded in the neural monitoring of internal organs, such as the heart. We measured with magnetoencephalograhy neural responses evoked by heartbeats while human participants freely mind-wandered. When interrupted by a visual stimulus at random intervals, participants scored the self-relatedness of the interrupted thought. They evaluated their involvement as the first-person perspective subject or agent in the thought ("I"), and on another scale to what degree they were thinking about themselves ("Me"). During the interrupted thought, neural responses to heartbeats in two regions of the DN, the ventral precuneus and the ventromedial prefrontal cortex, covaried, respectively, with the "I" and the "Me" dimensions of the self, even at the single-trial level. No covariation between self-relatedness and peripheral autonomic measures (heart rate, heart rate variability, pupil diameter, electrodermal activity, respiration rate, and phase) or alpha power was observed. Our results reveal a direct link between selfhood and neural responses to heartbeats in the DN and thus directly support theories grounding selfhood in the neural monitoring of visceral inputs. More generally, the tight functional coupling between self-related processing and cardiac monitoring observed here implies that, even in the absence of measured changes in peripheral bodily measures, physiological and cognitive functions have to be considered jointly in the DN. The default network (DN) has been consistently associated with self-processing but also with autonomic regulation. We hypothesized that these two functions could be functionally coupled in the DN, inspired by theories according to which selfhood is

  15. Neural Responses to Heartbeats in the Default Network Encode the Self in Spontaneous Thoughts

    PubMed Central

    Babo-Rebelo, Mariana; Richter, Craig G.

    2016-01-01

    The default network (DN) has been consistently associated with self-related cognition, but also to bodily state monitoring and autonomic regulation. We hypothesized that these two seemingly disparate functional roles of the DN are functionally coupled, in line with theories proposing that selfhood is grounded in the neural monitoring of internal organs, such as the heart. We measured with magnetoencephalograhy neural responses evoked by heartbeats while human participants freely mind-wandered. When interrupted by a visual stimulus at random intervals, participants scored the self-relatedness of the interrupted thought. They evaluated their involvement as the first-person perspective subject or agent in the thought (“I”), and on another scale to what degree they were thinking about themselves (“Me”). During the interrupted thought, neural responses to heartbeats in two regions of the DN, the ventral precuneus and the ventromedial prefrontal cortex, covaried, respectively, with the “I” and the “Me” dimensions of the self, even at the single-trial level. No covariation between self-relatedness and peripheral autonomic measures (heart rate, heart rate variability, pupil diameter, electrodermal activity, respiration rate, and phase) or alpha power was observed. Our results reveal a direct link between selfhood and neural responses to heartbeats in the DN and thus directly support theories grounding selfhood in the neural monitoring of visceral inputs. More generally, the tight functional coupling between self-related processing and cardiac monitoring observed here implies that, even in the absence of measured changes in peripheral bodily measures, physiological and cognitive functions have to be considered jointly in the DN. SIGNIFICANCE STATEMENT The default network (DN) has been consistently associated with self-processing but also with autonomic regulation. We hypothesized that these two functions could be functionally coupled in the DN, inspired by

  16. A comparison of polynomial approximations and artificial neural nets as response surfaces

    NASA Technical Reports Server (NTRS)

    Carpenter, William C.; Barthelemy, Jean-Francois M.

    1992-01-01

    Artificial neural nets and polynomial approximations were used to develop response surfaces for several test problems. Based on the number of functional evaluations required to build the approximations and the number of undetermined parameters associated with the approximations, the performance of the two types of approximations was found to be comparable. A rule of thumb is developed for determining the number of nodes to be used on a hidden layer of an artificial neural net, and the number of designs needed to train an approximation is discussed.

  17. Neural responses to facial expression and face identity in the monkey amygdala.

    PubMed

    Gothard, K M; Battaglia, F P; Erickson, C A; Spitler, K M; Amaral, D G

    2007-02-01

    The amygdala is purported to play an important role in face processing, yet the specificity of its activation to face stimuli and the relative contribution of identity and expression to its activation are unknown. In the current study, neural activity in the amygdala was recorded as monkeys passively viewed images of monkey faces, human faces, and objects on a computer monitor. Comparable proportions of neurons responded selectively to images from each category. Neural responses to monkey faces were further examined to determine whether face identity or facial expression drove the face-selective responses. The majority of these neurons (64%) responded both to identity and facial expression, suggesting that these parameters are processed jointly in the amygdala. Large fractions of neurons, however, showed pure identity-selective or expression-selective responses. Neurons were selective for a particular facial expression by either increasing or decreasing their firing rate compared with the firing rates elicited by the other expressions. Responses to appeasing faces were often marked by significant decreases of firing rates, whereas responses to threatening faces were strongly associated with increased firing rate. Thus global activation in the amygdala might be larger to threatening faces than to neutral or appeasing faces.

  18. Development of neural responsivity to vocal sounds in higher level auditory cortex of songbirds

    PubMed Central

    Miller-Sims, Vanessa C.

    2014-01-01

    Like humans, songbirds learn vocal sounds from “tutors” during a sensitive period of development. Vocal learning in songbirds therefore provides a powerful model system for investigating neural mechanisms by which memories of learned vocal sounds are stored. This study examined whether NCM (caudo-medial nidopallium), a region of higher level auditory cortex in songbirds, serves as a locus where a neural memory of tutor sounds is acquired during early stages of vocal learning. NCM neurons respond well to complex auditory stimuli, and evoked activity in many NCM neurons habituates such that the response to a stimulus that is heard repeatedly decreases to approximately one-half its original level (stimulus-specific adaptation). The rate of neural habituation serves as an index of familiarity, being low for familiar sounds, but high for novel sounds. We found that response strength across different song stimuli was higher in NCM neurons of adult zebra finches than in juveniles, and that only adult NCM responded selectively to tutor song. The rate of habituation across both tutor song and novel conspecific songs was lower in adult than in juvenile NCM, indicating higher familiarity and a more persistent response to song stimuli in adults. In juvenile birds that have memorized tutor vocal sounds, neural habituation was higher for tutor song than for a familiar conspecific song. This unexpected result suggests that the response to tutor song in NCM at this age may be subject to top-down influences that maintain the tutor song as a salient stimulus, despite its high level of familiarity. PMID:24694936

  19. Neural systems for social cognition: gray matter volume abnormalities in boys at high genetic risk of autism symptoms, and a comparison with idiopathic autism spectrum disorder.

    PubMed

    Goddard, Marcia N; Swaab, Hanna; Rombouts, Serge A R B; van Rijn, Sophie

    2016-09-01

    Klinefelter syndrome (47, XXY) is associated with several physical, cognitive, and behavioral consequences. In terms of social development, there is an increased risk of autism symptomatology. However, it remains unclear how social deficits are related to abnormal brain development and to what degree underlying mechanisms of social dysfunction in 47, XXY are similar to, or different from, those in idiopathic autism (ASD). This study was aimed at investigating the neural architecture of brain structures related to social information processing in boys with 47, XXY, also in comparison with boys with idiopathic ASD. MRI scans of 16 boys with 47, XXY, 16 with ASD, and 16 nonclinical, male controls were analyzed using voxel-based morphometry (VBM). A region of interest mask containing the superior temporal cortex, amygdala, orbitofrontal cortex (OFC), insular cortex, and medial frontal cortex was used. The Social Responsiveness Scale (SRS) was used to assess degree of autism spectrum symptoms. The 47, XXY group could not be distinguished from the ASD group on mean SRS scores, and their scores were significantly higher than in controls. VBM showed that boys with 47, XXY have significant gray matter volume reductions in the left and right insula, and the left OFC, compared with controls and boys with ASD. Additionally, boys with 47, XXY had significantly less gray matter in the right superior temporal gyrus than controls. These results imply social challenges associated with 47, XXY may be rooted in neural anatomy, and autism symptoms in boys with 47, XXY and boys with ASD might have, at least partially, different underlying etiologies.

  20. Neural Correlates of Antidepressant Treatment Response in Adolescents with Major Depressive Disorder

    PubMed Central

    Klimes-Dougan, Bonnie; Vu, Dung Pham; Westlund Schreiner, Melinda; Mueller, Bryon A.; Eberly, Lynn E.; Camchong, Jazmin; Westervelt, Ana; Lim, Kelvin O.

    2016-01-01

    Abstract Objective: The neural changes underlying response to antidepressant treatment in adolescents are unknown. Identification of neural change correlates of treatment response could (1) aid in understanding mechanisms of depression and its treatment and (2) serve as target biomarkers for future research. Method: Using functional magnetic resonance imaging, we examined changes in brain activation and functional connectivity in 13 unmedicated adolescents with major depressive disorder (MDD) before and after receiving treatment with a selective serotonin reuptake inhibitor medication for 8 weeks. Specifically, we examined brain activation during a negative emotion task and resting-state functional connectivity (RSFC), focusing on the amygdala to capture networks relevant to negative emotion. We conducted whole-brain analyses to identify how symptom improvement was related to change in brain activation during a negative emotion task or amygdala RSFC. Results: After treatment, clinical improvement was associated with decreased task activation in rostral and subgenual anterior cingulate cortex and increased activation in bilateral insula, bilateral middle frontal cortices, right parahippocampus, and left cerebellum. Analysis of change in amygdala RSFC showed that treatment response was associated with increased amygdala RSFC with right frontal cortex, but decreased amygdala RSFC with right precuneus and right posterior cingulate cortex. Conclusion: The findings represent a foothold for advancing understanding of pathophysiology of MDD in adolescents by revealing the critical neural circuitry changes that underlie a positive response to a standard treatment. Although preliminary, the present study provides a research platform for future work needed to confirm these biomarkers at a larger scale before using them in future target engagement studies of novel treatments. PMID:27159204

  1. Expectation and Surprise Determine Neural Population Responses in the Ventral Visual Stream

    PubMed Central

    Egner, Tobias; Monti, Jim M.; Summerfield, Christopher

    2014-01-01

    Visual cortex is traditionally viewed as a hierarchy of neural feature detectors, with neural population responses being driven by bottom-up stimulus features. Conversely, “predictive coding” models propose that each stage of the visual hierarchy harbors two computationally distinct classes of processing unit: representational units that encode the conditional probability of a stimulus and provide predictions to the next lower level; and error units that encode the mismatch between predictions and bottom-up evidence, and forward prediction error to the next higher level. Predictive coding therefore suggests that neural population responses in category-selective visual regions, like the fusiform face area (FFA), reflect a summation of activity related to prediction (“face expectation”) and prediction error (“face surprise”), rather than a homogenous feature detection response. We tested the rival hypotheses of the feature detection and predictive coding models by collecting functional magnetic resonance imaging data from the FFA while independently varying both stimulus features (faces vs houses) and subjects’ perceptual expectations regarding those features (low vs medium vs high face expectation). The effects of stimulus and expectation factors interacted, whereby FFA activity elicited by face and house stimuli was indistinguishable under high face expectation and maximally differentiated under low face expectation. Using computational modeling, we show that these data can be explained by predictive coding but not by feature detection models, even when the latter are augmented with attentional mechanisms. Thus, population responses in the ventral visual stream appear to be determined by feature expectation and surprise rather than by stimulus features per se. PMID:21147999

  2. Relationship between neural response and adaptation selectivity to form and color: an ERP study.

    PubMed

    Rentzeperis, Ilias; Nikolaev, Andrey R; Kiper, Daniel C; van Leeuwen, Cees

    2012-01-01

    Adaptation is widely used as a tool for studying selectivity to visual features. In these studies it is usually assumed that the loci of feature selective neural responses and adaptation coincide. We used an adaptation paradigm to investigate the relationship between response and adaptation selectivity in event-related potentials (ERPs). ERPs were evoked by the presentation of colored Glass patterns in a form discrimination task. Response selectivities to form and, to some extent, color of the patterns were reflected in the C1 and N1 ERP components. Adaptation selectivity to color was reflected in N1 and was followed by a late (300-500 ms after stimulus onset) effect of form adaptation. Thus for form, response and adaptation selectivity were manifested in non-overlapping intervals. These results indicate that adaptation and response selectivity can be associated with different processes. Therefore, inferring selectivity from an adaptation paradigm requires analysis of both adaptation and neural response data.

  3. Modeling neural circuits in Parkinson's disease.

    PubMed

    Psiha, Maria; Vlamos, Panayiotis

    2015-01-01

    Parkinson's disease (PD) is caused by abnormal neural activity of the basal ganglia which are connected to the cerebral cortex in the brain surface through complex neural circuits. For a better understanding of the pathophysiological mechanisms of PD, it is important to identify the underlying PD neural circuits, and to pinpoint the precise nature of the crucial aberrations in these circuits. In this paper, the general architecture of a hybrid Multilayer Perceptron (MLP) network for modeling the neural circuits in PD is presented. The main idea of the proposed approach is to divide the parkinsonian neural circuitry system into three discrete subsystems: the external stimuli subsystem, the life-threatening events subsystem, and the basal ganglia subsystem. The proposed model, which includes the key roles of brain neural circuit in PD, is based on both feed-back and feed-forward neural networks. Specifically, a three-layer MLP neural network with feedback in the second layer was designed. The feedback in the second layer of this model simulates the dopamine modulatory effect of compacta on striatum.

  4. Saturation thresholds of evoked neural and hemodynamic responses in awake and asleep rats

    NASA Astrophysics Data System (ADS)

    Schei, Jennifer L.; Van Nortwick, Amy S.; Meighan, Peter C.; Rector, David M.

    2011-03-01

    Neural activation generates a hemodynamic response to the localized region replenishing nutrients to the area. Changes in vigilance state have been shown to alter the vascular response where the vascular response is muted during wake compared to quiet sleep. We tested the saturation thresholds of the neurovascular response in the auditory cortex during wake and sleep by chronically implanting rats with an EEG electrode, a light emitting diode (LED, 600 nm), and photodiode to simultaneously measure evoked response potentials (ERPs) and evoked hemodynamic responses. We stimulated the cortex with a single speaker click delivered at random intervals 2-13 s at varied stimulus intensities ranging from 45-80 dB. To further test the potential for activity related saturation, we sleep deprived animals for 2, 4, or 6 hours and recorded evoked responses during the first hour recovery period. With increasing stimulus intensity, integrated ERPs and evoked hemodynamic responses increased; however the hemodynamic response approached saturation limits at a lower stimulus intensity than the ERP. With longer periods of sleep deprivation, the integrated ERPs did not change but evoked hemodynamic responses decreased. There may be physical limits in cortical blood delivery and vascular compliance, and with extended periods of neural activity during wake, vessels may approach these limits.

  5. Social priming modulates the neural response to ostracism: a new exploratory approach.

    PubMed

    Hudac, Caitlin M

    2018-04-16

    The present study sought to evaluate whether social priming modulates neural responses to ostracism, such that making arbitrary interpersonal decisions increases the experience of social exclusion more than making arbitrary physical decisions. This exploratory event-related potential (ERP) study utilized the Lunchroom task, in which adults (N = 28) first selected one of two options that included either interpersonal or physical descriptors. Participants then received ostracism outcome feedback within a lunchroom scenario in which they were either excluded (e.g. sitting alone) or included (e.g. surrounded by others). While the N2 component was sensitive to priming decision condition, only the P3 component discriminated between ostracism decisions. Further inspection of the neural sources indicated that the amygdala, anterior cingulate cortex, and superior temporal gyrus were more engaged for exclusion than inclusion conditions during both N2 and P3 temporal windows. Evaluation of temporal source dynamics suggest that the effects of ostracism are predominant between 250-500 ms and were larger following interpersonal than physical decisions. These results suggest that being ostracized evokes a larger neural response that is modulated following priming of the social brain.

  6. Intelligence moderates neural responses to monetary reward and punishment.

    PubMed

    Hawes, Daniel R; DeYoung, Colin G; Gray, Jeremy R; Rustichini, Aldo

    2014-05-01

    The relations between intelligence (IQ) and neural responses to monetary gains and losses were investigated in a simple decision task. In 94 healthy adults, typical responses of striatal blood oxygen level-dependent (BOLD) signal after monetary reward and punishment were weaker for subjects with higher IQ. IQ-moderated differential responses to gains and losses were also found for regions in the medial prefrontal cortex, posterior cingulate cortex, and left inferior frontal cortex. These regions have previously been identified with the subjective utility of monetary outcomes. Analysis of subjects' behavior revealed a correlation between IQ and the extent to which choices were related to experienced decision outcomes in preceding trials. Specifically, higher IQ predicted behavior to be more strongly correlated with an extended period of previously experienced decision outcomes, whereas lower IQ predicted behavior to be correlated exclusively to the most recent decision outcomes. We link these behavioral and imaging findings to a theoretical model capable of describing a role for intelligence during the evaluation of rewards generated by unknown probabilistic processes. Our results demonstrate neural differences in how people of different intelligence respond to experienced monetary rewards and punishments. Our theoretical discussion offers a functional description for how these individual differences may be linked to choice behavior. Together, our results and model support the hypothesis that observed correlations between intelligence and preferences may be rooted in the way decision outcomes are experienced ex post, rather than deriving exclusively from how choices are evaluated ex ante.

  7. Mice with Tak1 deficiency in neural crest lineage exhibit cleft palate associated with abnormal tongue development.

    PubMed

    Song, Zhongchen; Liu, Chao; Iwata, Junichi; Gu, Shuping; Suzuki, Akiko; Sun, Cheng; He, Wei; Shu, Rong; Li, Lu; Chai, Yang; Chen, YiPing

    2013-04-12

    Cleft palate represents one of the most common congenital birth defects in humans. TGFβ signaling, which is mediated by Smad-dependent and Smad-independent pathways, plays a crucial role in regulating craniofacial development and patterning, particularly in palate development. However, it remains largely unknown whether the Smad-independent pathway contributes to TGFβ signaling function during palatogenesis. In this study, we investigated the function of TGFβ activated kinase 1 (Tak1), a key regulator of Smad-independent TGFβ signaling in palate development. We show that Tak1 protein is expressed in both the epithelium and mesenchyme of the developing palatal shelves. Whereas deletion of Tak1 in the palatal epithelium or mesenchyme did not give rise to a cleft palate defect, inactivation of Tak1 in the neural crest lineage using the Wnt1-Cre transgenic allele resulted in failed palate elevation and subsequently the cleft palate formation. The failure in palate elevation in Wnt1-Cre;Tak1(F/F) mice results from a malformed tongue and micrognathia, resembling human Pierre Robin sequence cleft of the secondary palate. We found that the abnormal tongue development is associated with Fgf10 overexpression in the neural crest-derived tongue tissue. The failed palate elevation and cleft palate were recapitulated in an Fgf10-overexpressing mouse model. The repressive effect of the Tak1-mediated noncanonical TGFβ signaling on Fgf10 expression was further confirmed by inhibition of p38, a downstream kinase of Tak1, in the primary cell culture of developing tongue. Tak1 thus functions to regulate tongue development by controlling Fgf10 expression and could represent a candidate gene for mutation in human PRS clefting.

  8. Influence of DAT1 and COMT variants on neural activation during response inhibition in adolescents with attention-deficit/hyperactivity disorder and healthy controls.

    PubMed

    van Rooij, D; Hoekstra, P J; Bralten, J; Hakobjan, M; Oosterlaan, J; Franke, B; Rommelse, N; Buitelaar, J K; Hartman, C A

    2015-11-01

    Impairment of response inhibition has been implicated in attention-deficit/hyperactivity disorder (ADHD). Dopamine neurotransmission has been linked to the behavioural and neural correlates of response inhibition. The current study aimed to investigate the relationship of polymorphisms in two dopamine-related genes, the catechol-O-methyltransferase gene (COMT) and the dopamine transporter gene (SLC6A3 or DAT1), with the neural and behavioural correlates of response inhibition. Behavioural and neural measures of response inhibition were obtained in 185 adolescents with ADHD, 111 of their unaffected siblings and 124 healthy controls (mean age 16.9 years). We investigated the association of DAT1 and COMT variants on task performance and whole-brain neural activation during response inhibition in a hypothesis-free manner. Additionally, we attempted to explain variance in previously found ADHD effects on neural activation during response inhibition using these DAT1 and COMT polymorphisms. The whole-brain analyses demonstrated large-scale neural activation changes in the medial and lateral prefrontal, subcortical and parietal regions of the response inhibition network in relation to DAT1 and COMT polymorphisms. Although these neural activation changes were associated with different task performance measures, no relationship was found between DAT1 or COMT variants and ADHD, nor did variants in these genes explain variance in the effects of ADHD on neural activation. These results suggest that dopamine-related genes play a role in the neurobiology of response inhibition. The limited associations between gene polymorphisms and task performance further indicate the added value of neural measures in linking genetic factors and behavioural measures.

  9. Memorable Audiovisual Narratives Synchronize Sensory and Supramodal Neural Responses

    PubMed Central

    2016-01-01

    Abstract Our brains integrate information across sensory modalities to generate perceptual experiences and form memories. However, it is difficult to determine the conditions under which multisensory stimulation will benefit or hinder the retrieval of everyday experiences. We hypothesized that the determining factor is the reliability of information processing during stimulus presentation, which can be measured through intersubject correlation of stimulus-evoked activity. We therefore presented biographical auditory narratives and visual animations to 72 human subjects visually, auditorily, or combined, while neural activity was recorded using electroencephalography. Memory for the narrated information, contained in the auditory stream, was tested 3 weeks later. While the visual stimulus alone led to no meaningful retrieval, this related stimulus improved memory when it was combined with the story, even when it was temporally incongruent with the audio. Further, individuals with better subsequent memory elicited neural responses during encoding that were more correlated with their peers. Surprisingly, portions of this predictive synchronized activity were present regardless of the sensory modality of the stimulus. These data suggest that the strength of sensory and supramodal activity is predictive of memory performance after 3 weeks, and that neural synchrony may explain the mnemonic benefit of the functionally uninformative visual context observed for these real-world stimuli. PMID:27844062

  10. Common and distinct neural mechanisms of attentional switching and response conflict.

    PubMed

    Kim, Chobok; Johnson, Nathan F; Gold, Brian T

    2012-08-21

    The human capacities for overcoming prepotent actions and flexibly switching between tasks represent cornerstones of cognitive control. Functional neuroimaging has implicated a diverse set of brain regions contributing to each of these cognitive control processes. However, the extent to which attentional switching and response conflict draw on shared or distinct neural mechanisms remains unclear. The current study examined the neural correlates of response conflict and attentional switching using event-related functional magnetic resonance imaging (fMRI) and a fully randomized 2×2 design. We manipulated an arrow-word version of the Stroop task to measure conflict and switching in the context of a single task decision, in response to a common set of stimuli. Under these common conditions, both behavioral and imaging data showed significant main effects of conflict and switching but no interaction. However, conjunction analyses identified frontal regions involved in both switching and response conflict, including the dorsal anterior cingulate cortex (dACC) and left inferior frontal junction. In addition, connectivity analyses demonstrated task-dependent functional connectivity patterns between dACC and inferior temporal cortex for attentional switching and between dACC and posterior parietal cortex for response conflict. These results suggest that the brain makes use of shared frontal regions, but can dynamically modulate the connectivity patterns of some of those regions, to deal with attentional switching and response conflict. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Intergroup relationships do not reduce racial bias in empathic neural responses to pain.

    PubMed

    Contreras-Huerta, Luis Sebastian; Hielscher, Emily; Sherwell, Chase S; Rens, Natalie; Cunnington, Ross

    2014-11-01

    Perceiving the pain of others activates similar neural structures to those involved in the direct experience of pain, including sensory and affective-motivational areas. Empathic responses can be modulated by race, such that stronger neural activation is elicited by the perception of pain in people of the same race compared with another race. In the present study, we aimed to identify when racial bias occurs in the time course of neural empathic responses to pain. We also investigated whether group affiliation could modulate the race effect. Using the minimal group paradigm, we assigned participants to one of two mixed-race teams. We examined event-related potentials from participants when viewing members of their own and the other team receiving painful or non-painful touch. We identified a significant racial bias in early ERP components at N1 over frontal electrodes, where Painful stimuli elicited a greater negative shift relative to Non-Painful stimuli in response to own race faces only. A long latency empathic response was also found at P3, where there was significant differentiation between Painful and Non-Painful stimuli regardless of Race or Group. There was no evidence that empathy-related brain activity was modulated by minimal group manipulation. These results support a model of empathy for pain that consists of early, automatic bias towards own-race empathic responses and a later top-down cognitive evaluation that does not differentiate between races and may ultimately lead to unbiased behaviour. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Reward-related neural responses are dependent on the beneficiary

    PubMed Central

    Güroğlu, Berna; de Water, Erik; Meuwese, Rosa; Koolschijn, P. Cédric; Peper, Jiska S.; Crone, Eveline A.

    2014-01-01

    Prior studies have suggested that positive social interactions are experienced as rewarding. Yet, it is not well understood how social relationships influence neural responses to other persons’ gains. In this study, we investigated neural responses during a gambling task in which healthy participants (N = 31; 18 females) could win or lose money for themselves, their best friend or a disliked other (antagonist). At the moment of receiving outcome, person-related activity was observed in the dorsal medial prefrontal cortex (dmPFC), precuneus and temporal parietal junction (TPJ), showing higher activity for friends and antagonists than for self, and this activity was independent of outcome. The only region showing an interaction between the person-participants played for and outcome was the ventral striatum. Specifically, the striatum was more active following gains than losses for self and friends, whereas for the antagonist this pattern was reversed. Together, these results show that, in a context with social and reward information, social aspects are processed in brain regions associated with social cognition (mPFC, TPJ), and reward aspects are processed in primary reward areas (striatum). Furthermore, there is an interaction of social and reward information in the striatum, such that reward-related activity was dependent on social relationship. PMID:23720575

  13. The effects of high-intensity exercise on neural responses to images of food.

    PubMed

    Crabtree, Daniel R; Chambers, Edward S; Hardwick, Robert M; Blannin, Andrew K

    2014-02-01

    Acute bouts of high-intensity exercise modulate peripheral appetite regulating hormones to transiently suppress hunger. However, the effects of physical activity on central appetite regulation have yet to be fully investigated. We used functional magnetic resonance imaging (fMRI) to compare neural responses to visual food stimuli after intense exercise and rest. Fifteen lean healthy men [mean ± SD age: 22.5 ± 3.1 y; mean ± SD body mass index (in kg/m(2)): 24.2 ± 2.4] completed two 60-min trials-exercise (EX; running at ∼70% maximum aerobic capacity) and a resting control trial (REST)-in a counterbalanced order. After each trial, an fMRI assessment was completed in which images of high- and low-calorie foods were viewed. EX significantly suppressed subjective appetite responses while increasing thirst and core-body temperature. Furthermore, EX significantly suppressed ghrelin concentrations and significantly enhanced peptide YY release. Neural responses to images of high-calorie foods significantly increased dorsolateral prefrontal cortex activation and suppressed orbitofrontal cortex (OFC) and hippocampus activation after EX compared with REST. After EX, low-calorie food images increased insula and putamen activation and reduced OFC activation compared with REST. Furthermore, left pallidum activity was significantly elevated after EX when low-calorie images were viewed and was suppressed when high-calorie images were viewed, and these responses correlated significantly with thirst. Exercise increases neural responses in reward-related regions of the brain in response to images of low-calorie foods and suppresses activation during the viewing of high-calorie foods. These central responses are associated with exercise-induced changes in peripheral signals related to appetite-regulation and hydration status. This trial was registered at www.clinicaltrials.gov as NCT01926431.

  14. Mortality salience enhances racial in-group bias in empathic neural responses to others' suffering.

    PubMed

    Li, Xiaoyang; Liu, Yi; Luo, Siyang; Wu, Bing; Wu, Xinhuai; Han, Shihui

    2015-09-01

    Behavioral research suggests that mortality salience (MS) leads to increased in-group identification and in-group favoritism in prosocial behavior. What remains unknown is whether and how MS influences brain activity that mediates emotional resonance with in-group and out-group members and is associated with in-group favoritism in helping behavior. The current work investigated MS effects on empathic neural responses to racial in-group and out-group members' suffering. Experiments 1 and 2 respectively recorded event related potentials (ERPs) and blood oxygen level dependent signals to pain/neutral expressions of Asian and Caucasian faces from Chinese adults who had been primed with MS or negative affect (NA). Experiment 1 found that an early frontal/central activity (P2) was more strongly modulated by pain vs. neutral expressions of Asian than Caucasian faces, but this effect was not affected by MS vs. NA priming. However, MS relative to NA priming enhanced racial in-group bias in long-latency neural response to pain expressions over the central/parietal regions (P3). Experiment 2 found that MS vs. NA priming increased racial in-group bias in empathic neural responses to pain expression in the anterior and mid-cingulate cortex. Our findings indicate that reminding mortality enhances brain activity that differentiates between racial in-group and out-group members' emotional states and suggest a neural basis of in-group favoritism under mortality threat. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Neuroticism modulates the effects of intranasal vasopressin treatment on the neural response to positive and negative social interactions.

    PubMed

    Feng, Chunliang; DeMarco, Ashley C; Haroon, Ebrahim; Rilling, James K

    2015-07-01

    Neuroticism is a fundamental personality trait associated with proneness to feel negative affect. Here we ask how Neuroticism influences the neural response to positive and negative social interactions and how Neuroticism modulates the effect of intranasal oxytocin (OT) and vasopressin (AVP) on the neural response to social interactions. In a double-blind, placebo-controlled study, 153 male participants were randomized to receive 24 IU intranasal OT, 20 IU AVP or placebo. Afterwards, they were imaged with fMRI while playing an iterated Prisoner's Dilemma Game. On a different day, subjects completed the NEO personality inventory to measure Neuroticism. Neuroticism was positively correlated with the neural response to negative social interactions in the anterior cingulate cortex/medial prefrontal cortex and with the neural response to positive social interactions in the insula, indicating that Neuroticism modulates neuropsychological processing of both negative and positive social interactions. Neuroticism did not modulate the effect of intranasal OT treatment on the neural response to either positive or negative social interactions. On the other hand, AVP treatment significantly interacted with Neuroticism to modulate the BOLD response to both positive and negative social interactions. Specifically, AVP increased anterior cingulate cortex/medial prefrontal cortex and lateral temporal lobe responses to negative social interactions to a greater extent in participants scoring high rather than low on Neuroticism. AVP also increased the insula response to positive social interactions to a greater extent in participants scoring high rather than low on Neuroticism. These results imply that AVP may increase emotion regulation in response to negative social interactions and the salience of positive social interactions to a greater extent in individuals high compared to low in Neuroticism. The current findings urge caution against uniform clinical application of nonapeptides

  16. Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder

    PubMed Central

    van Zuiden, Mirjam; Koch, Saskia B.J.; Frijling, Jessie L.; Veltman, Dick J.; Olff, Miranda

    2017-01-01

    Abstract Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. PMID:27614769

  17. Meis2 is essential for cranial and cardiac neural crest development.

    PubMed

    Machon, Ondrej; Masek, Jan; Machonova, Olga; Krauss, Stefan; Kozmik, Zbynek

    2015-11-06

    TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging. We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2α-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities. Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.

  18. Sex differences in neural responses to stress and alcohol context cues.

    PubMed

    Seo, Dongju; Jia, Zhiru; Lacadie, Cheryl M; Tsou, Kristen A; Bergquist, Keri; Sinha, Rajita

    2011-11-01

    Stress and alcohol context cues are each associated with alcohol-related behaviors, yet neural responses underlying these processes remain unclear. This study investigated the neural correlates of stress and alcohol context cue experiences and examined sex differences in these responses. Using functional magnetic resonance imaging, brain responses were examined while 43 right-handed, socially drinking, healthy individuals (23 females) engaged in brief guided imagery of personalized stress, alcohol-cue, and neutral-relaxing scenarios. Stress and alcohol-cue exposure increased activity in the cortico-limbic-striatal circuit (P < 0.01, corrected), encompassing the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), left anterior insula, striatum, and visuomotor regions (parietal and occipital lobe, and cerebellum). Activity in the left dorsal striatum increased during stress, while bilateral ventral striatum activity was evident during alcohol-cue exposure. Men displayed greater stress-related activations in the mPFC, rostral ACC, posterior insula, amygdala, and hippocampus than women, whereas women showed greater alcohol-cue-related activity in the superior and middle frontal gyrus (SFG/MFG) than men. Stress-induced anxiety was positively associated with activity in emotion-modulation regions, including the medial OFC, ventromedial PFC, left superior-mPFC, and rostral ACC in men, but in women with activation in the SFG/MFG, regions involved in cognitive processing. Alcohol craving was significantly associated with the striatum (encompassing dorsal, and ventral) in men, supporting its involvement in alcohol "urge" in healthy men. These results indicate sex differences in neural processing of stress and alcohol-cue experiences and have implications for sex-specific vulnerabilities to stress- and alcohol-related psychiatric disorders. Copyright © 2010 Wiley-Liss, Inc.

  19. Neural differentiation of mesenchymal stem cells influences chemotactic responses to HGF.

    PubMed

    Zheng, Bing; Wang, Chunyan; He, Lihong; Xu, Xiaojing; Qu, Jing; Hu, Jun; Zhang, Huanxiang

    2013-01-01

    Recently, mesenchymal stem cells (MSCs) have been extensively used for cell-based therapies in neuronal degenerative disease. Although much effort has been devoted to the delineation of factors involved in the migration of MSCs, the relationship between the chemotactic responses and the differentiation status of these cells remains elusive. Here, we report that MSCs in varying neural differentiation states display different chemotactic responses to hepatocyte growth factor (HGF): first, the number of chemotaxing MSCs and the optimal concentrations of HGF that induced the peak migration varied greatly; second, time-lapse video analysis showed that MSCs in certain differentiation state migrated more efficiently toward HGF; third, the phosphorylation levels of Akt, ERK1/2, SAPK/JNK, and p38MAPK were closely related to the differentiation levels of MSCs subjected to HGF; and finally, although inhibition of ERK1/2 signaling significantly attenuated HGF-stimulated transfilter migration of both undifferentiated and differentiating MSCs, abolishment of PI3K/Akt, p38MAPK, or SAPK/JNK signaling only decreased the number of migrated cells in certain differentiation state(s). Blocking of PI3K/Akt or MAPK signaling impaired the migration efficiency and/or speed, the extent of which depends on the cell differentiation states. Meanwhile, F-actin rearrangement, which is essential for MSCs chemotaxis, was induced by HGF, and the time points of cytoskeletal reorganization were different among these cells. Collectively, these results demonstrate that neural differentiation of MSCs influences their chemotactic responses to HGF: MSCs in varying differentiation states possess different migratory capacities, thereby shedding light on optimization of the therapeutic potential of MSCs to be employed for neural regeneration after injury. Copyright © 2012 Wiley Periodicals, Inc.

  20. A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses.

    PubMed

    Jensen, Karin B; Kaptchuk, Ted J; Chen, Xiaoyan; Kirsch, Irving; Ingvar, Martin; Gollub, Randy L; Kong, Jian

    2015-10-01

    Fundamental aspects of human behavior operate outside of conscious awareness. Yet, theories of conditioned responses in humans, such as placebo and nocebo effects on pain, have a strong emphasis on conscious recognition of contextual cues that trigger the response. Here, we investigated the neural pathways involved in nonconscious activation of conditioned pain responses, using functional magnetic resonance imaging in healthy participants. Nonconscious compared with conscious activation of conditioned placebo analgesia was associated with increased activation of the orbitofrontal cortex, a structure with direct connections to affective brain regions and basic reward processing. During nonconscious nocebo, there was increased activation of the thalamus, amygdala, and hippocampus. In contrast to previous assumptions about conditioning in humans, our results show that conditioned pain responses can be elicited independently of conscious awareness and our results suggest a hierarchical activation of neural pathways for nonconscious and conscious conditioned responses. Demonstrating that the human brain has a nonconscious mechanism for responding to conditioned cues has major implications for the role of associative learning in behavioral medicine and psychiatry. Our results may also open up for novel approaches to translational animal-to-human research since human consciousness and animal cognition is an inherent paradox in all behavioral science. © The Author 2014. Published by Oxford University Press.

  1. Gamma band oscillations: a key to understanding schizophrenia symptoms and neural circuit abnormalities.

    PubMed

    McNally, James M; McCarley, Robert W

    2016-05-01

    We review our current understanding of abnormal γ band oscillations in schizophrenia, their association with symptoms and the underlying cortical circuit abnormality, with a particular focus on the role of fast-spiking parvalbumin gamma-aminobutyric acid (GABA) neurons in the disease state. Clinical electrophysiological studies of schizophrenia patients and pharmacological models of the disorder show an increase in spontaneous γ band activity (not stimulus-evoked) measures. These findings provide a crucial link between preclinical and clinical work examining the role of γ band activity in schizophrenia. MRI-based experiments measuring cortical GABA provides evidence supporting impaired GABAergic neurotransmission in schizophrenia patients, which is correlated with γ band activity level. Several studies suggest that stimulation of the cortical circuitry, directly or via subcortical structures, has the potential to modulate cortical γ activity, and improve cognitive function. Abnormal γ band activity is observed in patients with schizophrenia and disease models in animals, and is suggested to underlie the psychosis and cognitive/perceptual deficits. Convergent evidence from both clinical and preclinical studies suggest the central factor in γ band abnormalities is impaired GABAergic neurotransmission, particularly in a subclass of neurons which express parvalbumin. Rescue of γ band abnormalities presents an intriguing option for therapeutic intervention.

  2. Gamma band oscillations: a key to understanding schizophrenia symptoms and neural circuit abnormalities

    PubMed Central

    McNally, James M.; McCarley, Robert W.

    2016-01-01

    Purpose of review We review our current understanding of abnormal γ band oscillations in schizophrenia, their association with symptoms and the underlying cortical circuit abnormality, with a particular focus on the role of fast-spiking parvalbumin gamma-aminobutyric acid (GABA) neurons in the disease state. Recent findings Clinical electrophysiological studies of schizophrenia patients and pharmacological models of the disorder show an increase in spontaneous γ band activity (not stimulus-evoked) measures. These findings provide a crucial link between preclinical and clinical work examining the role of γ band activity in schizophrenia. MRI-based experiments measuring cortical GABA provides evidence supporting impaired GABAergic neurotransmission in schizophrenia patients, which is correlated with γ band activity level. Several studies suggest that stimulation of the cortical circuitry, directly or via subcortical structures, has the potential to modulate cortical γ activity, and improve cognitive function. Summary Abnormal γ band activity is observed in patients with schizophrenia and disease models in animals, and is suggested to underlie the psychosis and cognitive/perceptual deficits. Convergent evidence from both clinical and preclinical studies suggest the central factor in γ band abnormalities is impaired GABAergic neurotransmission, particularly in a subclass of neurons which express parvalbumin. Rescue of γ band abnormalities presents an intriguing option for therapeutic intervention. PMID:26900672

  3. Altered neural activation during prepotent response inhibition in breast cancer survivors treated with chemotherapy: an fMRI study.

    PubMed

    Kam, Julia W Y; Boyd, Lara A; Hsu, Chun L; Liu-Ambrose, Teresa; Handy, Todd C; Lim, Howard J; Hayden, Sherri; Campbell, Kristin L

    2016-09-01

    While impairments in executive functions have been reported in breast cancer survivors (BCS) who have undergone adjuvant chemotherapy, only a limited number of functional neuroimaging studies have associated alterations in cerebral activity with executive functions deficits in BCS. Using fMRI, the current study assessed the neural basis underlying a specific facet of executive function, namely prepotent response inhibition. 12 BCS who self-reported cognitive problems up to 3 years following cancer treatment and 12 female healthy comparisons (HC) performed the Stroop task. We compared their neural activation between the incongruent and neutral experimental conditions. Relative to the HC group, BCS showed lower blood-oxygen level dependent signal in several frontal regions, including the anterior cingulate cortex, a region critical for response inhibition. Our data indicates reduced neural activation in BCS during a prepotent response inhibition task, providing support for the prevailing notion of neural alterations observed in BCS treated with chemotherapy.

  4. Influence of SLC6A3 and COMT Variation on Neural Activation During Response Inhibition

    PubMed Central

    Congdon, Eliza; Constable, R. Todd; Lesch, Klaus Peter; Canli, Turhan

    2009-01-01

    There is evidence concerning the neural and genetic correlates of inhibitory control, but there have been limited attempts to combine this information. This study tested the hypothesis that two dopaminergic polymorphisms, SLC6A3 and COMT, influence neural activation during response inhibition. Healthy adults were genotyped for these polymorphisms and performed a measure of response inhibition while undergoing functional magnetic resonance imaging (fMRI). Results support the role of key frontostriatal regions underlying response inhibition. Furthermore, results support a significant influence of SLC6A3 and COMT variants on neural activity during inhibition, with greater activation during inhibition in carriers of the SLC6A3 9-allele or the COMT met-allele as compared to carriers of the SLC6A3 10/10 genotype or the COMT val/val genotype. These results add to a growing literature suggesting that inhibitory control is sensitive to variation in dopamine function, and suggest that this variation may be detectable at the level of individuals’ genotypes. PMID:19482231

  5. Computer-assisted cervical cancer screening using neural networks.

    PubMed

    Mango, L J

    1994-03-15

    A practical and effective system for the computer-assisted screening of conventionally prepared cervical smears is presented and described. Recent developments in neural network technology have made computerized analysis of the complex cellular scenes found on Pap smears possible. The PAPNET Cytological Screening System uses neural networks to automatically analyze conventional smears by locating and recognizing potentially abnormal cells. It then displays images of these objects for review and final diagnosis by qualified cytologists. The results of the studies presented indicate that the PAPNET system could be a useful tool for both the screening and rescreening of cervical smears. In addition, the system has been shown to be sensitive to some types of abnormalities which have gone undetected during manual screening.

  6. Roman Catholic beliefs produce characteristic neural responses to moral dilemmas

    PubMed Central

    Flexas, Albert; de Miguel, Pedro; Cela-Conde, Camilo J.; Munar, Enric

    2014-01-01

    This study provides exploratory evidence about how behavioral and neural responses to standard moral dilemmas are influenced by religious belief. Eleven Catholics and 13 Atheists (all female) judged 48 moral dilemmas. Differential neural activity between the two groups was found in precuneus and in prefrontal, frontal and temporal regions. Furthermore, a double dissociation showed that Catholics recruited different areas for deontological (precuneus; temporoparietal junction) and utilitarian moral judgments [dorsolateral prefrontal cortex (DLPFC); temporal poles], whereas Atheists did not (superior parietal gyrus for both types of judgment). Finally, we tested how both groups responded to personal and impersonal moral dilemmas: Catholics showed enhanced activity in DLPFC and posterior cingulate cortex during utilitarian moral judgments to impersonal moral dilemmas and enhanced responses in anterior cingulate cortex and superior temporal sulcus during deontological moral judgments to personal moral dilemmas. Our results indicate that moral judgment can be influenced by an acquired set of norms and conventions transmitted through religious indoctrination and practice. Catholic individuals may hold enhanced awareness of the incommensurability between two unequivocal doctrines of the Catholic belief set, triggered explicitly in a moral dilemma: help and care in all circumstances—but thou shalt not kill. PMID:23160812

  7. Roman Catholic beliefs produce characteristic neural responses to moral dilemmas.

    PubMed

    Christensen, Julia F; Flexas, Albert; de Miguel, Pedro; Cela-Conde, Camilo J; Munar, Enric

    2014-02-01

    This study provides exploratory evidence about how behavioral and neural responses to standard moral dilemmas are influenced by religious belief. Eleven Catholics and 13 Atheists (all female) judged 48 moral dilemmas. Differential neural activity between the two groups was found in precuneus and in prefrontal, frontal and temporal regions. Furthermore, a double dissociation showed that Catholics recruited different areas for deontological (precuneus; temporoparietal junction) and utilitarian moral judgments [dorsolateral prefrontal cortex (DLPFC); temporal poles], whereas Atheists did not (superior parietal gyrus for both types of judgment). Finally, we tested how both groups responded to personal and impersonal moral dilemmas: Catholics showed enhanced activity in DLPFC and posterior cingulate cortex during utilitarian moral judgments to impersonal moral dilemmas and enhanced responses in anterior cingulate cortex and superior temporal sulcus during deontological moral judgments to personal moral dilemmas. Our results indicate that moral judgment can be influenced by an acquired set of norms and conventions transmitted through religious indoctrination and practice. Catholic individuals may hold enhanced awareness of the incommensurability between two unequivocal doctrines of the Catholic belief set, triggered explicitly in a moral dilemma: help and care in all circumstances-but thou shalt not kill.

  8. Manipulations of cognitive strategies and intergroup relationships reduce the racial bias in empathic neural responses.

    PubMed

    Sheng, Feng; Han, Shihui

    2012-07-16

    Social relationships affect empathy in humans such that empathic neural responses to perceived pain were stronger to racial in-group members than to racial out-group members. Why does the racial bias in empathy (RBE) occur and how can we reduce it? We hypothesized that perceiving an other-race person as a symbol of a racial group, rather than as an individual, decreases references to his/her personal situation and weakens empathy for that person. This hypothesis predicts that individuating other-race persons by increasing attention to each individual's feelings or enclosing other-race individuals within one's own social group can reduce the RBE by increasing empathic neural responses to other-race individuals. In Experiment 1, we recorded event related brain potentials from Chinese adults as they made race judgments on Asian and Caucasian faces with pain or neutral expressions. We identified the RBE by showing that, relative to neutral expressions, pain expressions increased neural responses at 128-188 ms after stimulus onset over the frontal/central brain regions, and this effect was evident for same-race faces but not for other-race faces. Experiments 2 and 3 found that paying attention to observed individual's feelings of pain and including other-race individuals in one's own team for competitions respectively eliminated the RBE by increasing neural responses to pain expressions in other-race faces. Our results indicate that the RBE is not inevitable and that manipulations of both cognitive strategies and intergroup relationships can decrease RBE-related brain activity. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Differential neural responses to food images in women with bulimia versus anorexia nervosa.

    PubMed

    Brooks, Samantha J; O'Daly, Owen G; Uher, Rudolf; Friederich, Hans-Christoph; Giampietro, Vincent; Brammer, Michael; Williams, Steven C R; Schiöth, Helgi B; Treasure, Janet; Campbell, Iain C

    2011-01-01

    Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.

  10. Motor Control Abnormalities in Parkinson’s Disease

    PubMed Central

    Mazzoni, Pietro; Shabbott, Britne; Cortés, Juan Camilo

    2012-01-01

    The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb’s position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID:22675667

  11. Upper esophageal sphincter abnormalities: frequent finding on high-resolution esophageal manometry and associated with poorer treatment response in achalasia.

    PubMed

    Chavez, Yamile H; Ciarleglio, Maria M; Clarke, John O; Nandwani, Monica; Stein, Ellen; Roland, Bani C

    2015-01-01

    Abnormalities of the upper esophageal sphincter (UES) on high-resolution esophageal manometry (HREM) have been observed in both symptomatic and asymptomatic individuals and are often interpreted as incidental findings of unclear clinical significance. Our primary aims were: (1) to assess the frequency of UES abnormalities in consecutive patients referred for HREM studies; and (2) to characterize the demographics, clinical symptoms, and manometric profiles associated with UES abnormalities as compared with those with normal UES function. We performed a retrospective study of 200 consecutive patients referred for HREM. Patients were divided into those with normal and abnormal UES function, including impaired relaxation (residual pressure >12 mm Hg), hypertensive (>104 mm Hg), and hypotensive (<34 mm Hg) resting pressure. Clinical and manometric profiles were compared. A total of 32.5% of patients had UES abnormalities, the majority of which were hypertensive (55.4%). Patients with achalasia were significantly more likely to have UES abnormalities as compared with normal UES function (57.2% vs. 42.9%, P=0.04), with the most frequent abnormality being a hypertensive UES (50%). In addition, patients with impaired lower esophageal sphincter (LES) relaxation (esophagogastric junction outflow obstruction or achalasia) were more likely to have an UES abnormality present as compared with those with normal LES relaxation (53.1% vs. 28.6%, P=0.01). When we assessed for treatment response among patients with achalasia, we found that subjects with evidence of UES dysfunction had significantly worse treatment outcomes as compared with those without UES abnormalities present (20% improved vs. 100%, P=0.015). This remained true even after adjusting for type of treatment received (surgical myotomy, per-oral endoscopic mytotomy, botulinum toxin injection, pneumatic dilatation, medical therapy, P=0.67) and achalasia subtype (P=1.00). UES abnormalities are a frequent finding on HREM

  12. Abnormal autonomic and associated brain activities during rest in autism spectrum disorder

    PubMed Central

    Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T.; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R.

    2014-01-01

    Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916

  13. Reward-related neural responses are dependent on the beneficiary.

    PubMed

    Braams, Barbara R; Güroğlu, Berna; de Water, Erik; Meuwese, Rosa; Koolschijn, P Cédric; Peper, Jiska S; Crone, Eveline A

    2014-07-01

    Prior studies have suggested that positive social interactions are experienced as rewarding. Yet, it is not well understood how social relationships influence neural responses to other persons' gains. In this study, we investigated neural responses during a gambling task in which healthy participants (N = 31; 18 females) could win or lose money for themselves, their best friend or a disliked other (antagonist). At the moment of receiving outcome, person-related activity was observed in the dorsal medial prefrontal cortex (dmPFC), precuneus and temporal parietal junction (TPJ), showing higher activity for friends and antagonists than for self, and this activity was independent of outcome. The only region showing an interaction between the person-participants played for and outcome was the ventral striatum. Specifically, the striatum was more active following gains than losses for self and friends, whereas for the antagonist this pattern was reversed. Together, these results show that, in a context with social and reward information, social aspects are processed in brain regions associated with social cognition (mPFC, TPJ), and reward aspects are processed in primary reward areas (striatum). Furthermore, there is an interaction of social and reward information in the striatum, such that reward-related activity was dependent on social relationship. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  14. Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder.

    PubMed

    Nawijn, Laura; van Zuiden, Mirjam; Koch, Saskia B J; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2017-02-01

    Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. © The Author (2016). Published by Oxford University Press.

  15. Hyaluronic acid-laminin hydrogels increase neural stem cell transplant retention and migratory response to SDF-1α.

    PubMed

    Addington, C P; Dharmawaj, S; Heffernan, J M; Sirianni, R W; Stabenfeldt, S E

    2017-07-01

    The chemokine SDF-1α plays a critical role in mediating stem cell response to injury and disease and has specifically been shown to mobilize neural progenitor/stem cells (NPSCs) towards sites of neural injury. Current neural transplant paradigms within the brain suffer from low rates of retention and engraftment after injury. Therefore, increasing transplant sensitivity to injury-induced SDF-1α represents a method for increasing neural transplant efficacy. Previously, we have reported on a hyaluronic acid-laminin based hydrogel (HA-Lm gel) that increases NPSC expression of SDF-1α receptor, CXCR4, and subsequently, NPSC chemotactic migration towards a source of SDF-1α in vitro. The study presented here investigates the capacity of the HA-Lm gel to promote NPSC response to exogenous SDF-1α in vivo. We observed the HA-Lm gel to significantly increase NPSC transplant retention and migration in response to SDF-1α in a manner critically dependent on signaling via the SDF-1α-CXCR4 axis. This work lays the foundation for development of a more effective cell therapy for neural injury, but also has broader implications in the fields of tissue engineering and regenerative medicine given the essential roles of SDF-1α across injury and disease states. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Improved system identification using artificial neural networks and analysis of individual differences in responses of an identified neuron.

    PubMed

    Costalago Meruelo, Alicia; Simpson, David M; Veres, Sandor M; Newland, Philip L

    2016-03-01

    Mathematical modelling is used routinely to understand the coding properties and dynamics of responses of neurons and neural networks. Here we analyse the effectiveness of Artificial Neural Networks (ANNs) as a modelling tool for motor neuron responses. We used ANNs to model the synaptic responses of an identified motor neuron, the fast extensor motor neuron, of the desert locust in response to displacement of a sensory organ, the femoral chordotonal organ, which monitors movements of the tibia relative to the femur of the leg. The aim of the study was threefold: first to determine the potential value of ANNs as tools to model and investigate neural networks, second to understand the generalisation properties of ANNs across individuals and to different input signals and third, to understand individual differences in responses of an identified neuron. A metaheuristic algorithm was developed to design the ANN architectures. The performance of the models generated by the ANNs was compared with those generated through previous mathematical models of the same neuron. The results suggest that ANNs are significantly better than LNL and Wiener models in predicting specific neural responses to Gaussian White Noise, but not significantly different when tested with sinusoidal inputs. They are also able to predict responses of the same neuron in different individuals irrespective of which animal was used to develop the model, although notable differences between some individuals were evident. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Responsibility modulates the neural correlates of regret during the sequential risk-taking task.

    PubMed

    Li, Lin; Liu, Zhiyuan; Niu, Huanghuang; Zheng, Li; Cheng, Xuemei; Sun, Peng; Zhou, Fanzhi Anita; Guo, Xiuyan

    2018-03-01

    Responsibility is a necessary prerequisite in the experience of regret. The present fMRI study investigated the modulation of responsibility on the neural correlates of regret during a sequential risk-taking task. Participants were asked to open a series of boxes consecutively and decided when to stop. Each box contained a reward, except for one containing a devil to zero participant's gain in the trial. Once participants stopped, both collected gains and missed chances were revealed. We manipulated responsibility by setting two different contexts. In the Self (high responsibility) context, participants opened boxes and decided when to stop by themselves. In the Computer (low responsibility) context, a computer program opened boxes and decided when to stop for participants. Before each trial, participants were required to decide whether it would be a Self or a Computer context. Behaviorally, participants felt less regret (more relief) for gain outcome and more regret for the loss outcome in the high-responsibility context than low responsibility context. At the neural level, when experiencing a gain, high-responsibility trials were characterized by stronger activation in mPFC, pgACC, mOFC, and striatum with decreasing number of missed chances relative to low responsibility trials. When experiencing a loss, low responsibility trials were associated with stronger activation in dACC and bilateral insula than high-responsibility trials. Conversely, during a loss, high-responsibility trials showed more striatum activity than low responsibility trials. These results highlighted the sensitivity of the frontal region, striatum, and insula to changes in level of responsibility.

  18. Abnormal Size-Dependent Modulation of Motion Perception in Children with Autism Spectrum Disorder (ASD).

    PubMed

    Sysoeva, Olga V; Galuta, Ilia A; Davletshina, Maria S; Orekhova, Elena V; Stroganova, Tatiana A

    2017-01-01

    Excitation/Inhibition (E/I) imbalance in neural networks is now considered among the core neural underpinnings of autism psychopathology. In motion perception at least two phenomena critically depend on E/I balance in visual cortex: spatial suppression (SS), and spatial facilitation (SF) corresponding to impoverished or improved motion perception with increasing stimuli size, respectively. While SS is dominant at high contrast, SF is evident for low contrast stimuli, due to the prevalence of inhibitory contextual modulations in the former, and excitatory ones in the latter case. Only one previous study (Foss-Feig et al., 2013) investigated SS and SF in Autism Spectrum Disorder (ASD). Our study aimed to replicate previous findings, and to explore the putative contribution of deficient inhibitory influences into an enhanced SF index in ASD-a cornerstone for interpretation proposed by Foss-Feig et al. (2013). The SS and SF were examined in 40 boys with ASD, broad spectrum of intellectual abilities (63 < IQ < 127) and 44 typically developing (TD) boys, aged 6-15 years. The stimuli of small (1°) and large (12°) radius were presented under high (100%) and low (1%) contrast conditions. Social Responsiveness Scale and Sensory Profile Questionnaire were used to assess the autism severity and sensory processing abnormalities. We found that the SS index was atypically reduced, while SF index abnormally enhanced in children with ASD. The presence of abnormally enhanced SF in children with ASD was the only consistent finding between our study and that of Foss-Feig et al. While the SS and SF indexes were strongly interrelated in TD participants, this correlation was absent in their peers with ASD. In addition, the SF index but not the SS index correlated with the severity of autism and the poor registration abilities. The pattern of results is partially consistent with the idea of hypofunctional inhibitory transmission in visual areas in ASD. Nonetheless, the absence of

  19. Abnormal Size-Dependent Modulation of Motion Perception in Children with Autism Spectrum Disorder (ASD)

    PubMed Central

    Sysoeva, Olga V.; Galuta, Ilia A.; Davletshina, Maria S.; Orekhova, Elena V.; Stroganova, Tatiana A.

    2017-01-01

    Excitation/Inhibition (E/I) imbalance in neural networks is now considered among the core neural underpinnings of autism psychopathology. In motion perception at least two phenomena critically depend on E/I balance in visual cortex: spatial suppression (SS), and spatial facilitation (SF) corresponding to impoverished or improved motion perception with increasing stimuli size, respectively. While SS is dominant at high contrast, SF is evident for low contrast stimuli, due to the prevalence of inhibitory contextual modulations in the former, and excitatory ones in the latter case. Only one previous study (Foss-Feig et al., 2013) investigated SS and SF in Autism Spectrum Disorder (ASD). Our study aimed to replicate previous findings, and to explore the putative contribution of deficient inhibitory influences into an enhanced SF index in ASD—a cornerstone for interpretation proposed by Foss-Feig et al. (2013). The SS and SF were examined in 40 boys with ASD, broad spectrum of intellectual abilities (63 < IQ < 127) and 44 typically developing (TD) boys, aged 6–15 years. The stimuli of small (1°) and large (12°) radius were presented under high (100%) and low (1%) contrast conditions. Social Responsiveness Scale and Sensory Profile Questionnaire were used to assess the autism severity and sensory processing abnormalities. We found that the SS index was atypically reduced, while SF index abnormally enhanced in children with ASD. The presence of abnormally enhanced SF in children with ASD was the only consistent finding between our study and that of Foss-Feig et al. While the SS and SF indexes were strongly interrelated in TD participants, this correlation was absent in their peers with ASD. In addition, the SF index but not the SS index correlated with the severity of autism and the poor registration abilities. The pattern of results is partially consistent with the idea of hypofunctional inhibitory transmission in visual areas in ASD. Nonetheless, the absence of

  20. Expressive suppression and neural responsiveness to nonverbal affective cues

    PubMed Central

    Petrican, Raluca; Rosenbaum, R. Shayna; Grady, Cheryl

    2016-01-01

    responsiveness to nonverbal affective cues, while also suggesting one explanation for the suppressors’ poorer cognitive performance in social situations. Moreover, our results point to a potential neural mechanism supporting the development and perpetuation of expressive suppression as an emotion regulation strategy. PMID:26365712

  1. Neural Mechanisms of Improvements in Social Motivation after Pivotal Response Treatment: Two Case Studies

    ERIC Educational Resources Information Center

    Voos, Avery C.; Pelphrey, Kevin A.; Tirrell, Jonathan; Bolling, Danielle Z.; Vander Wyk, Brent; Kaiser, Martha D.; McPartland, James C.; Volkmar, Fred R.; Ventola, Pamela

    2013-01-01

    Pivotal response treatment (PRT) is an empirically validated behavioral treatment that has widespread positive effects on communication, behavior, and social skills in young children with autism spectrum disorder (ASD). For the first time, functional magnetic resonance imaging was used to identify the neural correlates of successful response to…

  2. The neural dynamics of stimulus and response conflict processing as a function of response complexity and task demands

    PubMed Central

    Donohue, Sarah E.; Appelbaum, Lawrence G.; McKay, Cameron C.; Woldorff, Marty G.

    2016-01-01

    Both stimulus and response conflict can disrupt behavior by slowing response times and decreasing accuracy. Although several neural activations have been associated with conflict processing, it is unclear how specific any of these are to the type of stimulus conflict or the amount of response conflict. Here, we recorded electrical brain activity, while manipulating the type of stimulus conflict in the task (spatial [Flanker] versus semantic [Stroop]) and the amount of response conflict (two versus four response choices). Behaviorally, responses were slower to incongruent versus congruent stimuli across all task and response types, along with overall slowing for higher response-mapping complexity. The earliest incongruency-related neural effect was a short-duration frontally-distributed negativity at ~200 ms that was only present in the Flanker spatial-conflict task. At longer latencies, the classic fronto-central incongruency-related negativity ‘Ninc’ was observed for all conditions, which was larger and ~100 ms longer in duration with more response options. Further, the onset of the motor-related lateralized readiness potential (LRP) was earlier for the two vs. four response sets, indicating that smaller response sets enabled faster motor-response preparation. The late positive complex (LPC) was present in all conditions except the two-response Stroop task, suggesting this late conflict-related activity is not specifically related to task type or response-mapping complexity. Importantly, across tasks and conditions, the LRP onset at or before the conflict-related Ninc, indicating that motor preparation is a rapid, automatic process that interacts with the conflict-detection processes after it has begun. Together, these data highlight how different conflict-related processes operate in parallel and depend on both the cognitive demands of the task and the number of response options. PMID:26827917

  3. The neural dynamics of stimulus and response conflict processing as a function of response complexity and task demands.

    PubMed

    Donohue, Sarah E; Appelbaum, Lawrence G; McKay, Cameron C; Woldorff, Marty G

    2016-04-01

    Both stimulus and response conflict can disrupt behavior by slowing response times and decreasing accuracy. Although several neural activations have been associated with conflict processing, it is unclear how specific any of these are to the type of stimulus conflict or the amount of response conflict. Here, we recorded electrical brain activity, while manipulating the type of stimulus conflict in the task (spatial [Flanker] versus semantic [Stroop]) and the amount of response conflict (two versus four response choices). Behaviorally, responses were slower to incongruent versus congruent stimuli across all task and response types, along with overall slowing for higher response-mapping complexity. The earliest incongruency-related neural effect was a short-duration frontally-distributed negativity at ~200 ms that was only present in the Flanker spatial-conflict task. At longer latencies, the classic fronto-central incongruency-related negativity 'N(inc)' was observed for all conditions, but was larger and ~100 ms longer in duration with more response options. Further, the onset of the motor-related lateralized readiness potential (LRP) was earlier for the two vs. four response sets, indicating that smaller response sets enabled faster motor-response preparation. The late positive complex (LPC) was present in all conditions except the two-response Stroop task, suggesting this late conflict-related activity is not specifically related to task type or response-mapping complexity. Importantly, across tasks and conditions, the LRP onset at or before the conflict-related N(inc), indicating that motor preparation is a rapid, automatic process that interacts with the conflict-detection processes after it has begun. Together, these data highlight how different conflict-related processes operate in parallel and depend on both the cognitive demands of the task and the number of response options. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Neural substrates of treatment response to cognitive-behavioral therapy in panic disorder with agoraphobia.

    PubMed

    Lueken, Ulrike; Straube, Benjamin; Konrad, Carsten; Wittchen, Hans-Ulrich; Ströhle, Andreas; Wittmann, André; Pfleiderer, Bettina; Uhlmann, Christina; Arolt, Volker; Jansen, Andreas; Kircher, Tilo

    2013-11-01

    Although exposure-based cognitive-behavioral therapy (CBT) is an effective treatment option for panic disorder with agoraphobia, the neural substrates of treatment response remain unknown. Evidence suggests that panic disorder with agoraphobia is characterized by dysfunctional safety signal processing. Using fear conditioning as a neurofunctional probe, the authors investigated neural baseline characteristics and neuroplastic changes after CBT that were associated with treatment outcome in patients with panic disorder with agoraphobia. Neural correlates of fear conditioning and extinction were measured using functional MRI before and after a manualized CBT program focusing on behavioral exposure in 49 medication-free patients with a primary diagnosis of panic disorder with agoraphobia. Treatment response was defined as a reduction exceeding 50% in Hamilton Anxiety Rating Scale scores. At baseline, nonresponders exhibited enhanced activation in the right pregenual anterior cingulate cortex, the hippocampus, and the amygdala in response to a safety signal. While this activation pattern partly resolved in nonresponders after CBT, successful treatment was characterized by increased right hippocampal activation when processing stimulus contingencies. Treatment response was associated with an inhibitory functional coupling between the anterior cingulate cortex and the amygdala that did not change over time. This study identified brain activation patterns associated with treatment response in patients with panic disorder with agoraphobia. Altered safety signal processing and anterior cingulate cortex-amygdala coupling may indicate individual differences among these patients that determine the effectiveness of exposure-based CBT and associated neuroplastic changes. Findings point to brain networks by which successful CBT in this patient population is mediated.

  5. Topsoil pollution forecasting using artificial neural networks on the example of the abnormally distributed heavy metal at Russian subarctic

    NASA Astrophysics Data System (ADS)

    Tarasov, D. A.; Buevich, A. G.; Sergeev, A. P.; Shichkin, A. V.; Baglaeva, E. M.

    2017-06-01

    Forecasting the soil pollution is a considerable field of study in the light of the general concern of environmental protection issues. Due to the variation of content and spatial heterogeneity of pollutants distribution at urban areas, the conventional spatial interpolation models implemented in many GIS packages mostly cannot provide appreciate interpolation accuracy. Moreover, the problem of prediction the distribution of the element with high variability in the concentration at the study site is particularly difficult. The work presents two neural networks models forecasting a spatial content of the abnormally distributed soil pollutant (Cr) at a particular location of the subarctic Novy Urengoy, Russia. A method of generalized regression neural network (GRNN) was compared to a common multilayer perceptron (MLP) model. The proposed techniques have been built, implemented and tested using ArcGIS and MATLAB. To verify the models performances, 150 scattered input data points (pollutant concentrations) have been selected from 8.5 km2 area and then split into independent training data set (105 points) and validation data set (45 points). The training data set was generated for the interpolation using ordinary kriging while the validation data set was used to test their accuracies. The networks structures have been chosen during a computer simulation based on the minimization of the RMSE. The predictive accuracy of both models was confirmed to be significantly higher than those achieved by the geostatistical approach (kriging). It is shown that MLP could achieve better accuracy than both kriging and even GRNN for interpolating surfaces.

  6. Abnormal response to methylphenidate across multiple fMRI procedures in cocaine use disorder: feasibility study.

    PubMed

    Moeller, Scott J; Konova, Anna B; Tomasi, Dardo; Parvaz, Muhammad A; Goldstein, Rita Z

    2016-07-01

    The indirect dopamine agonist methylphenidate remediates cognitive deficits in psychopathology, but the individual characteristics that determine its effects on the brain are not known. We aimed to determine whether targeted dopaminergically modulated traits and individual differences could predict neural response to methylphenidate across multiple functional magnetic resonance imaging (fMRI) procedures. We combined neural measures from three separate procedures (two inhibitory control tasks differing in their degree of emotional salience and resting-state functional connectivity) during methylphenidate (20 mg oral, versus randomized and counterbalanced placebo) and correlated these aggregated responses with cocaine use disorder diagnosis (22 cocaine abusers, 21 controls), symptoms of attention deficit hyperactivity disorder, and working memory capacity. Cocaine abusers, relative to controls, had a lower response in the dorsolateral prefrontal cortex to methylphenidate across all three procedures, driven by responses to the two inhibitory control tasks; reduced methylphenidate fMRI response in this region further correlated with more frequent cocaine use. Cocaine abuse (and its frequency), associated with lower tonic dopamine levels, correlated with a reduction in activation to methylphenidate (versus placebo). These initial results provide feasibility to the idea that multimodal fMRI tasks can be meaningfully aggregated, and that these aggregated procedures show a common disruption in addiction in a highly anticipated region relevant to cognitive control. Results also suggest that drug use frequency may represent an important modulatory variable in interpreting the efficacy of pharmacologically enhanced cognitive interventions in addiction.

  7. A differential neural response to threatening and non-threatening negative facial expressions in paranoid and non-paranoid schizophrenics.

    PubMed

    Phillips, M L; Williams, L; Senior, C; Bullmore, E T; Brammer, M J; Andrew, C; Williams, S C; David, A S

    1999-11-08

    Several studies have demonstrated impaired facial expression recognition in schizophrenia. Few have examined the neural basis for this; none have compared the neural correlates of facial expression perception in different schizophrenic patient subgroups. We compared neural responses to facial expressions in 10 right-handed schizophrenic patients (five paranoid and five non-paranoid) and five normal volunteers using functional Magnetic Resonance Imaging (fMRI). In three 5-min experiments, subjects viewed alternating 30-s blocks of black-and-white facial expressions of either fear, anger or disgust contrasted with expressions of mild happiness. After scanning, subjects categorised each expression. All patients were less accurate in identifying expressions, and showed less activation to these stimuli than normals. Non-paranoids performed poorly in the identification task and failed to activate neural regions that are normally linked with perception of these stimuli. They categorised disgust as either anger or fear more frequently than paranoids, and demonstrated in response to disgust expressions activation in the amygdala, a region associated with perception of fearful faces. Paranoids were more accurate in recognising expressions, and demonstrated greater activation than non-paranoids to most stimuli. We provide the first evidence for a distinction between two schizophrenic patient subgroups on the basis of recognition of and neural response to different negative facial expressions.

  8. Serotonin mediated immunoregulation and neural functions: Complicity in the aetiology of autism spectrum disorders.

    PubMed

    Jaiswal, Preeti; Mohanakumar, Kochupurackal P; Rajamma, Usha

    2015-08-01

    Serotonergic system has long been implicated in the aetiology of autism spectrum disorders (ASD), since platelet hyperserotonemia is consistently observed in a subset of autistic patients, who respond well to selective serotonin reuptake inhibitors. Apart from being a neurotransmitter, serotonin functions as a neurotrophic factor directing brain development and as an immunoregulator modulating immune responses. Serotonin transporter (SERT) regulates serotonin level in lymphoid tissues to ensure its proper functioning in innate and adaptive responses. Immunological molecules such as cytokines in turn regulate the transcription and activity of SERT. Dysregulation of serotonergic system could trigger signalling cascades that affect normal neural-immune interactions culminating in neurodevelopmental and neural connectivity defects precipitating behavioural abnormalities, or the disease phenotypes. Therefore, we suggest that a better understanding of the cross talk between serotonergic genes, immune systems and serotonergic neurotransmission will open wider avenues to develop pharmacological leads for addressing the core ASD behavioural deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Neural responses to kindness and malevolence differ in illness and recovery in women with anorexia nervosa.

    PubMed

    McAdams, Carrie J; Lohrenz, Terry; Montague, P Read

    2015-12-01

    In anorexia nervosa, problems with social relationships contribute to illness, and improvements in social support are associated with recovery. Using the multiround trust game and 3T MRI, we compare neural responses in a social relationship in three groups of women: women with anorexia nervosa, women in long-term weight recovery from anorexia nervosa, and healthy comparison women. Surrogate markers related to social signals in the game were computed each round to assess whether the relationship was improving (benevolence) or deteriorating (malevolence) for each subject. Compared with healthy women, neural responses to benevolence were diminished in the precuneus and right angular gyrus in both currently-ill and weight-recovered subjects with anorexia, but neural responses to malevolence differed in the left fusiform only in currently-ill subjects. Next, using a whole-brain regression, we identified an office assessment, the positive personalizing bias, that was inversely correlated with neural activity in the occipital lobe, the precuneus and posterior cingulate, the bilateral temporoparietal junctions, and dorsal anterior cingulate, during benevolence for all groups of subjects. The positive personalizing bias is a self-report measure that assesses the degree with which a person attributes positive experiences to other people. These data suggest that problems in perceiving kindness may be a consistent trait related to the development of anorexia nervosa, whereas recognizing malevolence may be related to recovery. Future work on social brain function, in both healthy and psychiatric populations, should consider positive personalizing biases as a possible marker of neural differences related to kindness perception. © 2015 Wiley Periodicals, Inc.

  10. Neural Responses to Kindness and Malevolence Differ in Illness and Recovery in Women With Anorexia Nervosa

    PubMed Central

    McAdams, Carrie J.; Lohrenz, Terry; Montague, P. Read

    2015-01-01

    In anorexia nervosa, problems with social relationships contribute to illness, and improvements in social support are associated with recovery. Using the multiround trust game and 3T MRI, we compare neural responses in a social relationship in three groups of women: women with anorexia nervosa, women in long-term weight recovery from anorexia nervosa, and healthy comparison women. Surrogate markers related to social signals in the game were computed each round to assess whether the relationship was improving (benevolence) or deteriorating (malevolence) for each subject. Compared with healthy women, neural responses to benevolence were diminished in the precuneus and right angular gyrus in both currently-ill and weight-recovered subjects with anorexia, but neural responses to malevolence differed in the left fusiform only in currently-ill subjects. Next, using a whole-brain regression, we identified an office assessment, the positive personalizing bias, that was inversely correlated with neural activity in the occipital lobe, the precuneus and posterior cingulate, the bilateral temporoparietal junctions, and dorsal anterior cingulate, during benevolence for all groups of subjects. The positive personalizing bias is a self-report measure that assesses the degree with which a person attributes positive experiences to other people. These data suggest that problems in perceiving kindness may be a consistent trait related to the development of anorexia nervosa, whereas recognizing malevolence may be related to recovery. Future work on social brain function, in both healthy and psychiatric populations, should consider positive personalizing biases as a possible marker of neural differences related to kindness perception. PMID:26416161

  11. Bounded Empathy: Neural Responses to Outgroup Targets’ (Mis)fortunes

    PubMed Central

    Cikara, Mina; Fiske, Susan T.

    2013-01-01

    The current study investigates whether mere stereotypes are sufficient to modulate empathic responses to other people’s (mis)fortunes, how these modulations manifest in the brain, and whether affective and neural responses relate to endorsing harm against different outgroup targets. Participants feel least bad when misfortunes befall envied targets, and worst when misfortunes befall pitied targets, as compared to ingroup targets. Participants are also least willing to endorse harming pitied targets, despite pitied targets being outgroup members. However, those participants who exhibit increased activation in functionally-defined insula/MFG when viewing pity targets experience positive events not only report feeling worse about those events, but also more willing to harm pity targets in a tradeoff scenario. Similarly, increased activation in anatomically-defined bilateral anterior insula, in response to positive events, predicts increased willingness to harm envy targets, but decreased willingness to harm ingroup targets, above and beyond self-reported affect in response to the events. Stereotypes’ specific content, and not just outgroup membership, modulates empathic responses and related behavioral consequences including harm. PMID:21671744

  12. Differential Neural Responses to Food Images in Women with Bulimia versus Anorexia Nervosa

    PubMed Central

    Brooks, Samantha J.; O′Daly, Owen G.; Uher, Rudolf; Friederich, Hans-Christoph; Giampietro, Vincent; Brammer, Michael; Williams, Steven C. R.; Schiöth, Helgi B.; Treasure, Janet; Campbell, Iain C.

    2011-01-01

    Background Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. Methods We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). Results In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Conclusions Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating. PMID:21799807

  13. Neural signatures of the response to emotional distraction: a review of evidence from brain imaging investigations

    PubMed Central

    Iordan, A. D.; Dolcos, S.; Dolcos, F.

    2013-01-01

    Prompt responses to emotional, potentially threatening, stimuli are supported by neural mechanisms that allow for privileged access of emotional information to processing resources. The existence of these mechanisms can also make emotional stimuli potent distracters, particularly when task-irrelevant. The ability to deploy cognitive control in order to cope with emotional distraction is essential for adaptive behavior, while reduced control may lead to enhanced emotional distractibility, which is often a hallmark of affective disorders. Evidence suggests that increased susceptibility to emotional distraction is linked to changes in the processing of emotional information that affect both the basic response to and coping with emotional distraction, but the neural correlates of these phenomena are not clear. The present review discusses emerging evidence from brain imaging studies addressing these issues, and highlights the following three aspects. First, the response to emotional distraction is associated with opposing patterns of activity in a ventral “hot” affective system (HotEmo, showing increased activity) and a dorsal “cold” executive system (ColdEx, showing decreased activity). Second, coping with emotional distraction involves top–down control in order to counteract the bottom-up influence of emotional distraction, and involves interactions between the amygdala and the prefrontal cortex. Third, both the response to and coping with emotional distraction are influenced by individual differences affecting emotional sensitivity and distractibility, which are linked to alterations of both HotEmo and ColdEx neural systems. Collectively, the available evidence identifies specific neural signatures of the response to emotional challenge, which are fundamental to understanding the mechanisms of emotion-cognition interactions in healthy functioning, and the changes linked to individual variation in emotional distractibility and susceptibility to affective

  14. Can we share the joy of others? Empathic neural responses to distress vs joy

    PubMed Central

    Perry, Daniella; Hendler, Talma

    2012-01-01

    The neural bases of empathy have been examined mainly in the context of reacting to others’ distress, while almost no attention has been paid to the mechanisms by which we share others’ joy. Using functional magnetic resonance imaging, we demonstrated that the same neural network mediates judgment of the emotional state of the other in response to both negative and positive events through empathy-related structures, such as the medial prefrontal cortex (MPFC), the insula, the superior temporal sulcus (STS) and the inferior frontal gyrus (IFG). However, the responses of the MPFC, bilateral insula and the right IFG to negative experiences occurring to the other (but not to the self) were found to be much more intense than the responses to positive experiences, indicating that humans have a remarkable ability to share the distress of others, but may react less to the joy of others. PMID:22156723

  15. Method for Constructing Composite Response Surfaces by Combining Neural Networks with Polynominal Interpolation or Estimation Techniques

    NASA Technical Reports Server (NTRS)

    Rai, Man Mohan (Inventor); Madavan, Nateri K. (Inventor)

    2007-01-01

    A method and system for data modeling that incorporates the advantages of both traditional response surface methodology (RSM) and neural networks is disclosed. The invention partitions the parameters into a first set of s simple parameters, where observable data are expressible as low order polynomials, and c complex parameters that reflect more complicated variation of the observed data. Variation of the data with the simple parameters is modeled using polynomials; and variation of the data with the complex parameters at each vertex is analyzed using a neural network. Variations with the simple parameters and with the complex parameters are expressed using a first sequence of shape functions and a second sequence of neural network functions. The first and second sequences are multiplicatively combined to form a composite response surface, dependent upon the parameter values, that can be used to identify an accurate mode

  16. Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Verhaak, Roel GW; Hoadley, Katherine A; Purdom, Elizabeth

    The Cancer Genome Atlas Network recently cataloged recurrent genomic abnormalities in glioblastoma multiforme (GBM). We describe a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrate multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, and PDGFRA/IDH1 each define the Classical, Mesenchymal, and Proneural subtypes, respectively. Gene signatures of normal brain cell types show a strong relationship between subtypes and different neural lineages. Additionally, response to aggressive therapy differs by subtype, with the greatest benefit in the Classical subtype and no benefitmore » in the Proneural subtype. We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies.« less

  17. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

    PubMed

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-06-07

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

  18. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals

    PubMed Central

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-01-01

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process. PMID:28590456

  19. [Neural activity related to emotional and empathic deficits in subjects with post-traumatic stress disorder who survived the L'Aquila (Central Italy) 2009 earthquake].

    PubMed

    Mazza, Monica; Pino, Maria Chiara; Tempesta, Daniela; Catalucci, Alessia; Masciocchi, Carlo; Ferrara, Michele

    2016-01-01

    Post-Traumatic Stress Disorder (PTSD) is a chronic anxiety disorder. The continued efforts to control the distressing memories by traumatized individuals, together with the reduction of responsiveness to the outside world, are called Emotional Numbing (EN). The EN is one of the central symptoms in PTSD and it plays an integral role not only in the development and maintenance of post-traumatic symptomatology, but also in the disability of emotional regulation. This disorder shows an abnormal response of cortical and limbic regions which are normally involved in understanding emotions since the very earliest stages of the development of processing ability. Patients with PTSD exhibit exaggerated brain responses to emotionally negative stimuli. Identifying the neural correlates of emotion regulation in these subjects is important for elucidating the neural circuitry involved in emotional and empathic dysfunction. We showed that PTSD patients, all survivors of the L'Aquila 2009 earthquake, have a higher sensitivity to negative emotion and lower empathy levels. These emotional and empathic deficits are accompanied by neural brain functional correlates. Indeed PTSD subjects exhibit functional abnormalities in brain regions that are involved in stress regulation and emotional responses. The reduced activation of the frontal areas and a stronger activation of the limbic areas when responding to emotional stimuli could lead the subjects to enact coping strategies aimed at protecting themselves from the re-experience of pain related to traumatic events. This would result in a dysfunctional hyperactivation of subcortical areas, which may cause emotional distress and, consequently, impaired social relationships often reported by PTSD patients.

  20. The reliability of nonlinear least-squares algorithm for data analysis of neural response activity during sinusoidal rotational stimulation in semicircular canal neurons.

    PubMed

    Ren, Pengyu; Li, Bowen; Dong, Shiyao; Chen, Lin; Zhang, Yuelin

    2018-01-01

    Although many mathematical methods were used to analyze the neural activity under sinusoidal stimulation within linear response range in vestibular system, the reliabilities of these methods are still not reported, especially in nonlinear response range. Here we chose nonlinear least-squares algorithm (NLSA) with sinusoidal model to analyze the neural response of semicircular canal neurons (SCNs) during sinusoidal rotational stimulation (SRS) over a nonlinear response range. Our aim was to acquire a reliable mathematical method for data analysis under SRS in vestibular system. Our data indicated that the reliability of this method in an entire SCNs population was quite satisfactory. However, the reliability was strongly negatively depended on the neural discharge regularity. In addition, stimulation parameters were the vital impact factors influencing the reliability. The frequency had a significant negative effect but the amplitude had a conspicuous positive effect on the reliability. Thus, NLSA with sinusoidal model resulted a reliable mathematical tool for data analysis of neural response activity under SRS in vestibular system and more suitable for those under the stimulation with low frequency but high amplitude, suggesting that this method can be used in nonlinear response range. This method broke out of the restriction of neural activity analysis under nonlinear response range and provided a solid foundation for future study in nonlinear response range in vestibular system.

  1. The reliability of nonlinear least-squares algorithm for data analysis of neural response activity during sinusoidal rotational stimulation in semicircular canal neurons

    PubMed Central

    Li, Bowen; Dong, Shiyao; Chen, Lin; Zhang, Yuelin

    2018-01-01

    Although many mathematical methods were used to analyze the neural activity under sinusoidal stimulation within linear response range in vestibular system, the reliabilities of these methods are still not reported, especially in nonlinear response range. Here we chose nonlinear least-squares algorithm (NLSA) with sinusoidal model to analyze the neural response of semicircular canal neurons (SCNs) during sinusoidal rotational stimulation (SRS) over a nonlinear response range. Our aim was to acquire a reliable mathematical method for data analysis under SRS in vestibular system. Our data indicated that the reliability of this method in an entire SCNs population was quite satisfactory. However, the reliability was strongly negatively depended on the neural discharge regularity. In addition, stimulation parameters were the vital impact factors influencing the reliability. The frequency had a significant negative effect but the amplitude had a conspicuous positive effect on the reliability. Thus, NLSA with sinusoidal model resulted a reliable mathematical tool for data analysis of neural response activity under SRS in vestibular system and more suitable for those under the stimulation with low frequency but high amplitude, suggesting that this method can be used in nonlinear response range. This method broke out of the restriction of neural activity analysis under nonlinear response range and provided a solid foundation for future study in nonlinear response range in vestibular system. PMID:29304173

  2. Girls' challenging social experiences in early adolescence predict neural response to rewards and depressive symptoms.

    PubMed

    Casement, Melynda D; Guyer, Amanda E; Hipwell, Alison E; McAloon, Rose L; Hoffmann, Amy M; Keenan, Kathryn E; Forbes, Erika E

    2014-04-01

    Developmental models of psychopathology posit that exposure to social stressors may confer risk for depression in adolescent girls by disrupting neural reward circuitry. The current study tested this hypothesis by examining the relationship between early adolescent social stressors and later neural reward processing and depressive symptoms. Participants were 120 girls from an ongoing longitudinal study of precursors to depression across adolescent development. Low parental warmth, peer victimization, and depressive symptoms were assessed when the girls were 11 and 12 years old, and participants completed a monetary reward guessing fMRI task and assessment of depressive symptoms at age 16. Results indicate that low parental warmth was associated with increased response to potential rewards in the medial prefrontal cortex (mPFC), striatum, and amygdala, whereas peer victimization was associated with decreased response to potential rewards in the mPFC. Furthermore, concurrent depressive symptoms were associated with increased reward anticipation response in mPFC and striatal regions that were also associated with early adolescent psychosocial stressors, with mPFC and striatal response mediating the association between social stressors and depressive symptoms. These findings are consistent with developmental models that emphasize the adverse impact of early psychosocial stressors on neural reward processing and risk for depression in adolescence. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Beyond static measures: A review of functional magnetic resonance spectroscopy and its potential to investigate dynamic glutamatergic abnormalities in schizophrenia.

    PubMed

    Jelen, Luke A; King, Sinead; Mullins, Paul G; Stone, James M

    2018-05-01

    Abnormalities of the glutamate system are increasingly implicated in schizophrenia but their exact nature remains unknown. Proton magnetic resonance spectroscopy ( 1 H-MRS), while fundamental in revealing glutamatergic alterations in schizophrenia, has, until recently, been significantly limited and thought to only provide static measures. Functional magnetic resonance spectroscopy (fMRS), which uses sequential scans for dynamic measurement of a range of brain metabolites in activated brain areas, has lately been applied to a variety of task or stimulus conditions, producing interesting insights into neurometabolite responses to neural activation. Here, we summarise the existing 1 H-MRS studies of brain glutamate in schizophrenia. We then present a comprehensive review of research studies that have utilised fMRS, and lastly consider how fMRS methods might further the understanding of glutamatergic abnormalities in schizophrenia.

  4. Neural Progenitor Cells Rptor Ablation Impairs Development but Benefits to Seizure-Induced Behavioral Abnormalities.

    PubMed

    Chen, Ling-Lin; Wu, Mei-Ling; Zhu, Feng; Kai, Jie-Jing; Dong, Jing-Yin; Wu, Xi-Mei; Zeng, Ling-Hui

    2016-12-01

    Previous study suggests that mTOR signaling pathway may play an important role in epileptogenesis. The present work was designed to explore the contribution of raptor protein to the development of epilepsy and comorbidities. Mice with conditional knockout of raptor protein were generated by cross-bred Rptor flox/flox mice with nestin-CRE mice. The expression of raptor protein was analyzed by Western blotting in brain tissue samples. Neuronal death and mossy fiber sprouting were detected by FJB staining and Timm staining, respectively. Spontaneous seizures were recorded by EEG-video system. Morris water maze, open field test, and excitability test were used to study the behaviors of Rptor CKO mice. As the consequence of deleting Rptor, downstream proteins of raptor in mTORC1 signaling were partly blocked. Rptor CKO mice exhibited decrease in body and brain weight under 7 weeks old and accordingly, cortical layer thickness. After kainic acid (KA)-induced status epilepticus, overactivation of mTORC1 signaling was markedly reversed in Rptor CKO mice. Although low frequency of spontaneous seizure and seldom neuronal cell death were observed in both Rptor CKO and control littermates, KA seizure-induced mossy fiber spouting were attenuated in Rptor CKO mice. Additionally, cognitive-deficit and anxiety-like behavior after KA-induced seizures were partly reversed in Rptor CKO mice. Loss of the Rptor gene in mice neural progenitor cells affects normal development in young age and may contribute to alleviate KA seizure-induced behavioral abnormalities, suggesting that raptor protein plays an important role in seizure comorbidities. © 2016 John Wiley & Sons Ltd.

  5. Tympanal mechanics and neural responses in the ears of a noctuid moth

    NASA Astrophysics Data System (ADS)

    Ter Hofstede, Hannah M.; Goerlitz, Holger R.; Montealegre-Z, Fernando; Robert, Daniel; Holderied, Marc W.

    2011-12-01

    Ears evolved in many groups of moths to detect the echolocation calls of predatory bats. Although the neurophysiology of bat detection has been intensively studied in moths for decades, the relationship between sound-induced movement of the noctuid tympanic membrane and action potentials in the auditory sensory cells (A1 and A2) has received little attention. Using laser Doppler vibrometry, we measured the velocity and displacement of the tympanum in response to pure tone pulses for moths that were intact or prepared for neural recording. When recording from the auditory nerve, the displacement of the tympanum at the neural threshold remained constant across frequencies, whereas velocity varied with frequency. This suggests that the key biophysical parameter for triggering action potentials in the sensory cells of noctuid moths is tympanum displacement, not velocity. The validity of studies on the neurophysiology of moth hearing rests on the assumption that the dissection and recording procedures do not affect the biomechanics of the ear. There were no consistent differences in tympanal velocity or displacement when moths were intact or prepared for neural recordings for sound levels close to neural threshold, indicating that this and other neurophysiological studies provide good estimates of what intact moths hear at threshold.

  6. Fitting PMT Responses with an Artificial Neural Network

    NASA Astrophysics Data System (ADS)

    Kemmerer, William; Niculescu, Gabriel

    2017-09-01

    Correctly modeling the low light responce of photodetectors such as photomultiplier tubes (PMT) is crucial for the operation of particle detection relying on the Cherenkov effect. The Gas Ring Imaging Cherenkov (GRINCH) in the SuperBigBite Spectrometer (SBS) at Jefferson Lab will rely on an array of 510 29 mm 9125B PMTs. To select the tubes for this array, more than 900 were tested and their low-light response function was fitted. An Artificial Neural Network was defined and trained to extract the relevant PMT parameters without carrying out a detailed fir of the ADC spectrum. These results will be discussed here. NSF.

  7. Autonomic and brain responses associated with empathy deficits in autism spectrum disorder

    PubMed Central

    Eilam‐Stock, Tehila; Zhou, Thomas; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Hof, Patrick R.; Friston, Karl J.

    2015-01-01

    Abstract Accumulating evidence suggests that autonomic signals and their cortical representations are closely linked to emotional processes, and that related abnormalities could lead to social deficits. Although socio‐emotional impairments are a defining feature of autism spectrum disorder (ASD), empirical evidence directly supporting the link between autonomic, cortical, and socio‐emotional abnormalities in ASD is still lacking. In this study, we examined autonomic arousal indexed by skin conductance responses (SCR), concurrent cortical responses measured by functional magnetic resonance imaging, and effective brain connectivity estimated by dynamic causal modeling in seventeen unmedicated high‐functioning adults with ASD and seventeen matched controls while they performed an empathy‐for‐pain task. Compared to controls, adults with ASD showed enhanced SCR related to empathetic pain, along with increased neural activity in the anterior insular cortex, although their behavioral empathetic pain discriminability was reduced and overall SCR was decreased. ASD individuals also showed enhanced correlation between SCR and neural activities in the anterior insular cortex. Importantly, significant group differences in effective brain connectivity were limited to greater reduction in the negative intrinsic connectivity of the anterior insular cortex in the ASD group, indicating a failure in attenuating anterior insular responses to empathetic pain. These results suggest that aberrant interoceptive precision, as indexed by abnormalities in autonomic activity and its central representations, may underlie empathy deficits in ASD. Hum Brain Mapp 36:3323–3338, 2015. © 2015 The Authors Human Brain Mapping Published byWiley Periodicals, Inc. PMID:25995134

  8. The missing link: Mothers’ neural response to infant cry related to infant attachment behaviors

    PubMed Central

    Laurent, Heidemarie K.; Ablow, Jennifer C.

    2012-01-01

    This study addresses a gap in the attachment literature by investigating maternal neural response to cry related to infant attachment classifications and behaviors. Twenty-two primiparous mothers and their 18-month old infants completed the Strange Situation Procedure (SS) to elicit attachment behaviors. During a separate functional MRI session, mothers were exposed to their own infant’s cry sound, as well as an unfamiliar infant’s cry and control sound. Maternal neural response to own infant cry related to both overall attachment security and specific infant behaviors. Mothers of less secure infants maintained greater activation to their cry in left parahippocampal and amygdala regions and the right posterior insula. consistent with a negative schematic response bias. Mothers of infants exhibiting more avoidant or contact maintaining behaviors during the SS showed diminished response across left prefrontal, parietal, and cerebellar areas involved in attentional processing and cognitive control. Mothers of infants exhibiting more disorganized behavior showed reduced response in bilateral temporal and subcallosal areas relevant to social cognition and emotion regulation. No differences by attachment classification were found. Implications for attachment transmission models are discussed. PMID:22982277

  9. The missing link: mothers' neural response to infant cry related to infant attachment behaviors.

    PubMed

    Laurent, Heidemarie K; Ablow, Jennifer C

    2012-12-01

    This study addresses a gap in the attachment literature by investigating maternal neural response to cry related to infant attachment classifications and behaviors. Twenty-two primiparous mothers and their 18-month old infants completed the Strange Situation (SS) procedure to elicit attachment behaviors. During a separate functional MRI session, mothers were exposed to their own infant's cry sound, as well as an unfamiliar infant's cry and control sound. Maternal neural response to own infant cry related to both overall attachment security and specific infant behaviors. Mothers of less secure infants maintained greater activation to their cry in left parahippocampal and amygdala regions and the right posterior insula consistent with a negative schematic response bias. Mothers of infants exhibiting more avoidant or contact maintaining behaviors during the SS showed diminished response across left prefrontal, parietal, and cerebellar areas involved in attentional processing and cognitive control. Mothers of infants exhibiting more disorganized behavior showed reduced response in bilateral temporal and subcallosal areas relevant to social cognition and emotion regulation. No differences by attachment classification were found. Implications for attachment transmission models are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Bilingualism increases neural response consistency and attentional control: Evidence for sensory and cognitive coupling

    PubMed Central

    Krizman, Jennifer; Skoe, Erika; Marian, Viorica; Kraus, Nina

    2014-01-01

    Auditory processing is presumed to be influenced by cognitive processes – including attentional control – in a top-down manner. In bilinguals, activation of both languages during daily communication hones inhibitory skills, which subsequently bolster attentional control. We hypothesize that the heightened attentional demands of bilingual communication strengthens connections between cognitive (i.e., attentional control) and auditory processing, leading to greater across-trial consistency in the auditory evoked response (i.e., neural consistency) in bilinguals. To assess this, we collected passively-elicited auditory evoked responses to the syllable [da] and separately obtained measures of attentional control and language ability in adolescent Spanish-English bilinguals and English monolinguals. Bilinguals demonstrated enhanced attentional control and more consistent brainstem and cortical responses. In bilinguals, but not monolinguals, brainstem consistency tracked with language proficiency and attentional control. We interpret these enhancements in neural consistency as the outcome of strengthened attentional control that emerged from experience communicating in two languages. PMID:24413593

  11. Detection of necrotic neural response in super-acute cerebral ischemia using activity-induced manganese-enhanced (AIM) MRI.

    PubMed

    Inoue, Yasuo; Aoki, Ichio; Mori, Yuki; Kawai, Yuko; Ebisu, Toshihiko; Osaka, Yasuhiko; Houri, Takashi; Mineura, Katsuyoshi; Higuchi, Toshihiro; Tanaka, Chuzo

    2010-04-01

    Immediate and certain determination of the treatable area is important for choosing risky treatments such as thrombolysis for brain ischemia, especially in the super-acute phase. Although it has been suggested that the mismatch between regions displaying 'large abnormal perfusion' and 'small abnormal diffusion' indicates a treatable area on an MRI, it has also been reported that the mismatch region is an imperfect approximation of the treatable region named the 'penumbra'. Manganese accumulation reflecting calcium influx into cells was reported previously in a middle cerebral artery occlusion (MCAO) model using activity-induced manganese-enhanced (AIM) MRI. However, in the super-acute phase, there have been no reports about mismatches between areas showing changes to the apparent diffusion coefficient (ADC) and regions that are enhanced in AIM MRI. It is expected that the AIM signal can be enhanced immediately after cerebral ischemia in the necrotic core region due to calcium influx. In this study, a remote embolic rat model, created using titanium-oxide macrospheres, was used to observe necrotic neural responses in the super-acute phase after ischemia. In addition, images were evaluated by comparison between ADC, AIM MRI, and histology. The signal enhancement in AIM MRI was detected at 2 min after the cerebral infarction using a remote embolic method. The enhanced area on the AIM MRI was significantly smaller than that on the ADC map. The tissue degeneration highlighted by histological analysis corresponded more closely to the enhanced area on the AIM MRI than that on the ADC map. Thus, the manganese-enhanced region in brain ischemia might indicate 'necrotic' irreversible tissue that underwent calcium influx. 2010 John Wiley & Sons, Ltd.

  12. A Data-Driven Response Virtual Sensor Technique with Partial Vibration Measurements Using Convolutional Neural Network.

    PubMed

    Sun, Shan-Bin; He, Yuan-Yuan; Zhou, Si-Da; Yue, Zhen-Jiang

    2017-12-12

    Measurement of dynamic responses plays an important role in structural health monitoring, damage detection and other fields of research. However, in aerospace engineering, the physical sensors are limited in the operational conditions of spacecraft, due to the severe environment in outer space. This paper proposes a virtual sensor model with partial vibration measurements using a convolutional neural network. The transmissibility function is employed as prior knowledge. A four-layer neural network with two convolutional layers, one fully connected layer, and an output layer is proposed as the predicting model. Numerical examples of two different structural dynamic systems demonstrate the performance of the proposed approach. The excellence of the novel technique is further indicated using a simply supported beam experiment comparing to a modal-model-based virtual sensor, which uses modal parameters, such as mode shapes, for estimating the responses of the faulty sensors. The results show that the presented data-driven response virtual sensor technique can predict structural response with high accuracy.

  13. A Data-Driven Response Virtual Sensor Technique with Partial Vibration Measurements Using Convolutional Neural Network

    PubMed Central

    Sun, Shan-Bin; He, Yuan-Yuan; Zhou, Si-Da; Yue, Zhen-Jiang

    2017-01-01

    Measurement of dynamic responses plays an important role in structural health monitoring, damage detection and other fields of research. However, in aerospace engineering, the physical sensors are limited in the operational conditions of spacecraft, due to the severe environment in outer space. This paper proposes a virtual sensor model with partial vibration measurements using a convolutional neural network. The transmissibility function is employed as prior knowledge. A four-layer neural network with two convolutional layers, one fully connected layer, and an output layer is proposed as the predicting model. Numerical examples of two different structural dynamic systems demonstrate the performance of the proposed approach. The excellence of the novel technique is further indicated using a simply supported beam experiment comparing to a modal-model-based virtual sensor, which uses modal parameters, such as mode shapes, for estimating the responses of the faulty sensors. The results show that the presented data-driven response virtual sensor technique can predict structural response with high accuracy. PMID:29231868

  14. Genetic disruption of CYP26B1 severely affects development of neural crest derived head structures, but does not compromise hindbrain patterning.

    PubMed

    Maclean, Glenn; Dollé, Pascal; Petkovich, Martin

    2009-03-01

    Cyp26b1 encodes a cytochrome-P450 enzyme that catabolizes retinoic acid (RA), a vitamin A derived signaling molecule. We have examined Cyp26b1(-/-) mice and report that mutants exhibit numerous abnormalities in cranial neural crest cell derived tissues. At embryonic day (E) 18.5 Cyp26b1(-/-) animals exhibit a truncated mandible, abnormal tooth buds, reduced ossification of calvaria, and are missing structures of the maxilla and nasal process. Some of these abnormalities may be due to defects in formation of Meckel's cartilage, which is truncated with an unfused distal region at E14.5 in mutant animals. Despite the severe malformations, we did not detect any abnormalities in rhombomere segmentation, or in patterning and migration of anterior hindbrain derived neural crest cells. Abnormal migration of neural crest cells toward the posterior branchial arches was observed, which may underlie defects in larynx and hyoid development. These data suggest different periods of sensitivity of anterior and posterior hindbrain neural crest derivatives to elevated levels of RA in the absence of CYP26B1. (c) 2009 Wiley-Liss, Inc.

  15. Monetary favors and their influence on neural responses and revealed preference

    PubMed Central

    Harvey, Ann H.; Kirk, Ulrich; Denfield, George H.; Montague, P. Read

    2010-01-01

    Favors from a sender to a receiver are known to bias decisions made by the recipient, especially when the decision relates to the sender – a feature of social exchange known as reciprocity. Using an art-viewing paradigm possessing no objectively correct answer for preferring one piece of art over another, we show that sponsorship of the experiment by a company endows the company’s logo with the capacity to bias revealed preference for art displayed next to the logo. Merely offering to sponsor the experiment similarly endowed the gesturing company’s logo with the capacity to bias revealed preferences. These effects do not depend upon the size of the displayed art or the proximity of the sponsoring logo to the piece of art. We used fMRI to show that such monetary favors do not modulate a special collection of brain responses, but instead modulate responses in neural networks normally activated by a wide range of preference judgments. The results raise the important possibility that monetary favors bias judgments in domains seemingly unrelated to the favor, but nevertheless act in an implicit way through neural networks that underlie normal, ongoing preference judgments. PMID:20631188

  16. Adolescents' behavioral and neural responses to e-cigarette advertising.

    PubMed

    Chen, Yvonnes; Fowler, Carina H; Papa, Vlad B; Lepping, Rebecca J; Brucks, Morgan G; Fox, Andrew T; Martin, Laura E

    2018-03-01

    Although adolescents are a group heavily targeted by the e-cigarette industry, research in cue-reactivity has not previously examined adolescents' behavioral and neural responses to e-cigarette advertising. This study addressed this gap through two experiments. In Experiment One, adult traditional cigarette smokers (n = 41) and non-smokers (n = 41) answered questions about e-cigarette and neutral advertising images. The 40 e-cigarette advertising images that most increased desire to use the product were matched to 40 neutral advertising images with similar content. In Experiment Two, the 80 advertising images selected in Experiment One were presented to adolescents (n = 30) during an functional magnetic resonance imaging brain scan. There was a range of traditional cigarette smoking across the sample with some adolescents engaging in daily smoking and others who had never smoked. Adolescents self-reported that viewing the e-cigarette advertising images increased their desire to smoke. Additionally, all participants regardless of smoking statuses showed significantly greater brain activation to e-cigarette advertisements in areas associated with cognitive control (left middle frontal gyrus), reward (right medial frontal gyrus), visual processing/attention (left lingual gyrus/fusiform gyrus, right inferior parietal lobule, left posterior cingulate, left angular gyrus) and memory (right parahippocampus, left insula). Further, an exploratory analysis showed that compared with age-matched non-smokers (n = 7), adolescent smokers (n = 7) displayed significantly greater neural activation to e-cigarette advertising images in the left inferior temporal gyrus/fusiform gyrus, compared with their responses to neutral advertising images. Overall, participants' brain responses to e-cigarette advertisements suggest a need to further investigate the long-run impact of e-cigarette advertising on adolescents. © 2017 Society for the Study of Addiction.

  17. A face a mother could love: depression-related maternal neural responses to infant emotion faces.

    PubMed

    Laurent, Heidemarie K; Ablow, Jennifer C

    2013-01-01

    Depressed mothers show negatively biased responses to their infants' emotional bids, perhaps due to faulty processing of infant cues. This study is the first to examine depression-related differences in mothers' neural response to their own infant's emotion faces, considering both effects of perinatal depression history and current depressive symptoms. Primiparous mothers (n = 22), half of whom had a history of major depressive episodes (with one episode occurring during pregnancy and/or postpartum), were exposed to images of their own and unfamiliar infants' joy and distress faces during functional neuroimaging. Group differences (depression vs. no-depression) and continuous effects of current depressive symptoms were tested in relation to neural response to own infant emotion faces. Compared to mothers with no psychiatric diagnoses, those with depression showed blunted responses to their own infant's distress faces in the dorsal anterior cingulate cortex. Mothers with higher levels of current symptomatology showed reduced responses to their own infant's joy faces in the orbitofrontal cortex and insula. Current symptomatology also predicted lower responses to own infant joy-distress in left-sided prefrontal and insula/striatal regions. These deficits in self-regulatory and motivational response circuits may help explain parenting difficulties in depressed mothers.

  18. The neural basis of responsibility attribution in decision-making.

    PubMed

    Li, Peng; Shen, Yue; Sui, Xue; Chen, Changming; Feng, Tingyong; Li, Hong; Holroyd, Clay

    2013-01-01

    Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent's emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context.

  19. The neural basis of responsive caregiving behaviour: Investigating temporal dynamics within the parental brain.

    PubMed

    Young, Katherine S; Parsons, Christine E; Stein, Alan; Vuust, Peter; Craske, Michelle G; Kringelbach, Morten L

    2017-05-15

    Whether it is the sound of a distressed cry or the image of a cute face, infants capture our attention. Parents and other adults alike are drawn into interactions to engage in play, nurturance and provide care. Responsive caregiving behaviour is a key feature of the parent-infant relationship, forming the foundation upon which attachment is built. Infant cues are considered to be 'innate releasers' or 'motivational entities' eliciting responses in nearby adults (Lorenz 1943; Murray, 1979) [42,43]. Through the advent of modern neuroimaging, we are beginning to understand the initiation of this motivational state at the neurobiological level. In this review, we first describe a current model of the 'parental brain', based on functional MRI studies assessing neural responses to infant cues. Next, we discuss recent findings from temporally sensitive techniques (magneto- and electroencephalography) that illuminate the temporal dynamics of this neural network. We focus on converging evidence highlighting a specific role for the orbitofrontal cortex in supporting rapid orienting responses to infant cues. In addition, we consider to what extent these neural processes are tied to parenthood, or whether they might be present universally in all adults. We highlight important avenues for future research, including utilizing multiple levels of analysis for a comprehensive understanding of adaptive caregiving behaviour. Finally, we discuss how this research can help us understand disrupted parent-infant relationships, such as in situations where parents' contingent responding to infant cues is disrupted; for example, in parental depression or anxiety where cognitive attentional processes are disrupted. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Turning on the alarm: the neural mechanisms of the transition from innocuous to painful sensation.

    PubMed

    Johnstone, Tom; Salomons, Tim V; Backonja, Miroslav Misha; Davidson, Richard J

    2012-01-16

    The experience of pain occurs when the level of a stimulus is sufficient to elicit a marked affective response, putatively to warn the organism of potential danger and motivate appropriate behavioral responses. Understanding the biological mechanisms of the transition from innocuous to painful levels of sensation is essential to understanding pain perception as well as clinical conditions characterized by abnormal relationships between stimulation and pain response. Thus, the primary objective of this study was to characterize the neural response associated with this transition and the correspondence between that response and subjective reports of pain. Towards this goal, this study examined BOLD response profiles across a range of temperatures spanning the pain threshold. 14 healthy adults underwent functional magnetic resonance imaging (fMRI) while a range of thermal stimuli (44-49°C) were applied. BOLD responses showed a sigmoidal profile along the range of temperatures in a network of brain regions including insula and mid-cingulate, as well as a number of regions associated with motor responses including ventral lateral nuclei of the thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD responses in these regions explained up to 85% of the variance in individual pain ratings, and yielded an estimate of the temperature of steepest transition from non-painful to painful heat that was nearly identical to that generated by subjective ratings. These results demonstrate a precise characterization of the relationship between objective levels of stimulation, resulting neural activation, and subjective experience of pain and provide direct evidence for a neural mechanism supporting the nonlinear transition from innocuous to painful levels along the sensory continuum. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Abnormal regional homogeneity and its correlations with personality in first-episode, treatment-naive somatization disorder.

    PubMed

    Song, Yan; Su, Qinji; Jiang, Muliang; Liu, Feng; Yao, Dapeng; Dai, Yi; Long, Liling; Yu, Miaoyu; Liu, Jianrong; Zhang, Zhikun; Zhang, Jian; Xiao, Changqing; Guo, Wenbin

    2015-08-01

    Structural and functional abnormalities of the default mode network (DMN) and their correlations with personality have been found in somatization disorder (SD). However, no study is conducted to identify regional neural activity and its correlations with personality in SD. In this study, regional homogeneity (ReHo) was applied to explore whether abnormal regional neural activity is present in patients with SD and its correlations with personality measured by Eysenck Personality Questionnaire (EPQ). Twenty-five first-episode, treatment-naive patients with SD and 28 sex-, age-, and education-matched healthy controls participated in the whole study. During the scanning, all subjects were instructed to lie still with their eyes closed and remain awake. A ReHo approach was employed to analyze the data. The SD group had a significantly increased ReHo in the left angular gyrus (AG) compared to healthy controls. The increased ReHo positively correlated to the neuroticism scores of EPQ (EPQ-N). No other correlations were detected between the ReHo values and other related factors, such as symptom severity and education level. Our results suggest that abnormal regional neural activity of the DMN may play a key role in SD with clinical implications and emphasize the importance of the DMN in the pathophysiological process of SD. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Effects of Oxytocin on Neural Response to Facial Expressions in Patients with Schizophrenia

    PubMed Central

    Shin, Na Young; Park, Hye Yoon; Jung, Wi Hoon; Park, Jin Woo; Yun, Je-Yeon; Jang, Joon Hwan; Kim, Sung Nyun; Han, Hyun Jung; Kim, So-Yeon; Kang, Do-Hyung; Kwon, Jun Soo

    2015-01-01

    Impaired facial emotion recognition is a core deficit in schizophrenia. Oxytocin has been shown to improve social perception in patients with schizophrenia; however, the effect of oxytocin on the neural activity underlying facial emotion recognition has not been investigated. This study was aimed to assess the effect of a single dose of intranasal oxytocin on brain activity in patients with schizophrenia using an implicit facial emotion-recognition paradigm. Sixteen male patients with schizophrenia and 16 age-matched healthy male control subjects participated in a randomized, double-blind, placebo-controlled crossover trial at Seoul National University Hospital. Delivery of a single dose of 40 IU intranasal oxytocin and the placebo was separated by 1 week. Drug conditions were compared by performing a region of interest (ROI) analysis of the bilateral amygdala on responses to the emotion recognition test. It was found that nasal spray decreased amygdala activity for fearful emotion and increased activity for happy faces. Further, oxytocin elicited differential effects between the patient and control groups. Intranasal oxytocin attenuated amygdala activity for emotional faces in patients with schizophrenia, whereas intranasal oxytocin significantly increased amygdala activity in healthy controls. Oxytocin-induced BOLD signal changes in amygdala in response to happy faces was related to attachment style in the control group. Our result provides new evidence of a modulatory effect of oxytocin on neural response to emotional faces for patients with schizophrenia. Future studies are needed to investigate the effectiveness of long-term treatment with intranasal oxytocin on neural activity in patients with schizophrenia. PMID:25666311

  3. Effects of Oxytocin on Neural Response to Facial Expressions in Patients with Schizophrenia.

    PubMed

    Shin, Na Young; Park, Hye Yoon; Jung, Wi Hoon; Park, Jin Woo; Yun, Je-Yeon; Jang, Joon Hwan; Kim, Sung Nyun; Han, Hyun Jung; Kim, So-Yeon; Kang, Do-Hyung; Kwon, Jun Soo

    2015-07-01

    Impaired facial emotion recognition is a core deficit in schizophrenia. Oxytocin has been shown to improve social perception in patients with schizophrenia; however, the effect of oxytocin on the neural activity underlying facial emotion recognition has not been investigated. This study was aimed to assess the effect of a single dose of intranasal oxytocin on brain activity in patients with schizophrenia using an implicit facial emotion-recognition paradigm. Sixteen male patients with schizophrenia and 16 age-matched healthy male control subjects participated in a randomized, double-blind, placebo-controlled crossover trial at Seoul National University Hospital. Delivery of a single dose of 40 IU intranasal oxytocin and the placebo was separated by 1 week. Drug conditions were compared by performing a region of interest (ROI) analysis of the bilateral amygdala on responses to the emotion recognition test. It was found that nasal spray decreased amygdala activity for fearful emotion and increased activity for happy faces. Further, oxytocin elicited differential effects between the patient and control groups. Intranasal oxytocin attenuated amygdala activity for emotional faces in patients with schizophrenia, whereas intranasal oxytocin significantly increased amygdala activity in healthy controls. Oxytocin-induced BOLD signal changes in amygdala in response to happy faces was related to attachment style in the control group. Our result provides new evidence of a modulatory effect of oxytocin on neural response to emotional faces for patients with schizophrenia. Future studies are needed to investigate the effectiveness of long-term treatment with intranasal oxytocin on neural activity in patients with schizophrenia.

  4. Neural responsivity during soft drink intake, anticipation, and advertisement exposure in habitually consuming youth.

    PubMed

    Burger, Kyle S; Stice, Eric

    2014-02-01

    Although soft drinks are heavily advertised, widely consumed, and have been associated with obesity, little is understood regarding neural responsivity to soft drink intake, anticipated intake, and advertisements. Functional MRI was used to assess examine neural response to carbonated soft drink intake, anticipated intake and advertisement exposure as well as milkshake intake in 27 adolescents that varied on soft drink consumer status. Intake and anticipated intake of carbonated Coke® activated regions implicated in gustatory, oral somatosensory, and reward processing, yet high-fat/sugar milkshake intake elicited greater activation in these regions vs. Coke intake. Advertisements highlighting the Coke product vs. nonfood control advertisements, but not the Coke logo, activated gustatory and visual brain regions. Habitual Coke consumers vs. nonconsumers showed greater posterior cingulate responsivity to Coke logo ads, suggesting that the logo is a conditioned cue. Coke consumers exhibited less ventrolateral prefrontal cortex responsivity during anticipated Coke intake relative to nonconsumers. Results indicate that soft drinks activate reward and gustatory regions, but are less potent in activating these regions than high-fat/sugar beverages, and imply that habitual soft drink intake promotes hyper-responsivity of regions encoding salience/attention toward brand specific cues and hypo-responsivity of inhibitory regions while anticipating intake. Copyright © 2013 The Obesity Society.

  5. Neural responsivity during soft drink intake, anticipation, and advertisement exposure in habitually consuming youth

    PubMed Central

    Burger, Kyle S.; Stice, Eric

    2014-01-01

    OBJECTIVE Although soft drinks are heavily advertised, widely consumed, and have been associated with obesity, little is understood regarding neural responsivity to soft drink intake, anticipated intake, and advertisements. METHODS Functional MRI was used to assess examine neural response to carbonated soft drink intake, anticipated intake and advertisement exposure as well as milkshake intake in 27 adolescents that varied on soft drink consumer status. RESULTS Intake and anticipated intake of carbonated Coke® activated regions implicated in gustatory, oral somatosensory, and reward processing, yet high-fat/sugar milkshake intake elicited greater activation in these regions versus Coke intake. Advertisements highlighting the Coke product vs. non-food control advertisements, but not the Coke logo, activated gustatory and visual brain regions. Habitual Coke consumers vs. non-consumers showed greater posterior cingulate responsivity to Coke logo ads, suggesting that the logo is a conditioned cue. Coke consumers exhibited less ventrolateral prefrontal cortex responsivity during anticipated Coke intake relative to non-consumers. CONCLUSIONS Results indicate that soft drinks activate reward and gustatory regions, but are less potent in activating these regions than high-fat/sugar beverages, and imply that habitual soft drink intake promotes hyper-responsivity of regions encoding salience/attention toward brand specific cues and hypo-responsivity of inhibitory regions while anticipating intake. PMID:23836764

  6. What Can Psychiatric Disorders Tell Us about Neural Processing of the Self?

    PubMed

    Zhao, Weihua; Luo, Lizhu; Li, Qin; Kendrick, Keith M

    2013-01-01

    Many psychiatric disorders are associated with abnormal self-processing. While these disorders also have a wide-range of complex, and often heterogeneous sets of symptoms involving different cognitive, emotional, and motor domains, an impaired sense of self can contribute to many of these. Research investigating self-processing in healthy subjects has facilitated identification of changes in specific neural circuits which may cause altered self-processing in psychiatric disorders. While there is evidence for altered self-processing in many psychiatric disorders, here we will focus on four of the most studied ones, schizophrenia, autism spectrum disorder (ASD), major depression, and borderline personality disorder (BPD). We review evidence for dysfunction in two different neural systems implicated in self-processing, namely the cortical midline system (CMS) and the mirror neuron system (MNS), as well as contributions from altered inter-hemispheric connectivity (IHC). We conclude that while abnormalities in frontal-parietal activity and/or connectivity in the CMS are common to all four disorders there is more disruption of integration between frontal and parietal regions resulting in a shift toward parietal control in schizophrenia and ASD which may contribute to the greater severity and delusional aspects of their symptoms. Abnormalities in the MNS and in IHC are also particularly evident in schizophrenia and ASD and may lead to disturbances in sense of agency and the physical self in these two disorders. A better future understanding of how changes in the neural systems sub-serving self-processing contribute to different aspects of symptom abnormality in psychiatric disorders will require that more studies carry out detailed individual assessments of altered self-processing in conjunction with measurements of neural functioning.

  7. Neural and Behavioral Responses during Self-Evaluative Processes Differ in Youth with and without Autism

    ERIC Educational Resources Information Center

    Pfeifer, Jennifer H.; Merchant, Junaid S.; Colich, Natalie L.; Hernandez, Leanna M.; Rudie, Jeff D.; Dapretto, Mirella

    2013-01-01

    This fMRI study investigated neural responses while making appraisals of self and other, across the social and academic domains, in children and adolescents with and without autism spectrum disorders (ASD). Compared to neurotypical youth, those with ASD exhibited hypoactivation of ventromedial prefrontal cortex during self-appraisals. Responses in…

  8. Augmented Indian hedgehog signaling in cranial neural crest cells leads to craniofacial abnormalities and dysplastic temporomandibular joint in mice

    PubMed Central

    Yang, Ling; Gu, Shuping; Ye, Wenduo; Song, Yingnan; Chen, YiPing

    2016-01-01

    Extensive studies have pinpointed the crucial role of Indian hedgehog (Ihh) signaling in the development of the appendicular skeleton and the essential function of Ihh in the formation of the temporomandibular joint (TMJ). In this study, we have investigated the effect of augmented Ihh signaling in TMJ development. We took a transgenic gain-of-function approach by overexpressing Ihh in the cranial neural crest (CNC) cells using a conditional Ihh transgenic allele and the Wnt1-Cre allele. We found that Wnt1-Cre-mediated tissue-specific overexpression of Ihh in the CNC lineage caused severe craniofacial abnormalities, including cleft lip/palate, encephalocele, anophthalmos, micrognathia, and defective TMJ development. In the mutant TMJ, the glenoid fossa was completely absent, whereas the condyle and the articular disc appeared relatively normal with slightly delayed chondrocyte differentiation. Our findings thus demonstrate that augmented Ihh signaling is detrimental to craniofacial development, and that finely tuned Ihh signaling is critical for TMJ formation. Our results also provide additional evidence that the development of the condyle and articular disc is independent of the glenoid fossa. PMID:26553654

  9. Intrathecal fentanyl abolishes the exaggerated blood pressure response to cycling in hypertensive men

    PubMed Central

    Barbosa, Thales C.; Vianna, Lauro C.; Fernandes, Igor A.; Prodel, Eliza; Rocha, Helena N. M.; Garcia, Vinicius P.; Rocha, Natalia G.; Secher, Niels H.

    2016-01-01

    Key points The increase in blood pressure observed during physical activities is exaggerated in patients with hypertension, exposing them to a higher cardiovascular risk.Neural signals from the skeletal muscles appear to be overactive, resulting in this abnormal response in hypertensive patients.In the present study, we tested whether the attenuation of these neural signals in hypertensive patients could normalize their abnormal increase in blood pressure during physical activity.Attenuation of the neural signals from the leg muscles with intrathecal fentanyl injection reduced the blood pressure of hypertensive men during cycling exercise to a level comparable to that of normotensive men.Skeletal muscle afferent overactivity causes the abnormal cardiovascular response to exercise and was reverted in this experimental model, appearing as potential target for treatment. Abstract Hypertensive patients present an exaggerated increase in blood pressure and an elevated cardiovascular risk during exercise. Although controversial, human studies suggest that group III and IV skeletal muscle afferents might contribute to this abnormal response. In the present study, we investigated whether attenuation of the group III and IV muscle afferent signal of hypertensive men eliminates the exaggerated increase in blood pressure occurring during exercise. Eight hypertensive men performed two sessions of 5 min of cycling exercise at 40 W. Between sessions, the subjects were provided with a lumbar intrathecal injection of fentanyl, a μ‐opioid receptor agonist, aiming to attenuate the central projection of opioid‐sensitive group III and IV muscle afferent nerves. The cardiovascular response to exercise of these subjects was compared with that of six normotensive men. During cycling, the hypertensive group demonstrated an exaggerated increase in blood pressure compared to the normotensive group (mean ± SEM: +17 ± 3 vs. +8 ± 1 mmHg, respectively; P < 0.05), whereas the

  10. An oxytocin-induced facilitation of neural and emotional responses to social touch correlates inversely with autism traits.

    PubMed

    Scheele, Dirk; Kendrick, Keith M; Khouri, Christoph; Kretzer, Elisa; Schläpfer, Thomas E; Stoffel-Wagner, Birgit; Güntürkün, Onur; Maier, Wolfgang; Hurlemann, René

    2014-08-01

    Social communication through touch and mutual grooming can convey highly salient socio-emotional signals and has been shown to involve the neuropeptide oxytocin (OXT) in several species. Less is known about the modulatory influence of OXT on the neural and emotional responses to human interpersonal touch. The present randomized placebo (PLC)-controlled within-subject pharmaco-functional magnetic resonance imaging (fMRI) study was designed to test the hypothesis that a single intranasal dose of synthetic OXT (24 IU) would facilitate both neural and emotional responses to interpersonal touch in a context- (female vs male touch) and trait- (autistic trait load) specific manner. Specifically, the experimental rationale was to manipulate the reward value of interpersonal touch independent of the intensity and type of actual cutaneous stimulation administered. Thus, 40 heterosexual males believed that they were touched by either a man or a woman, although in fact an identical pattern of touch was always given by the same female experimenter blind to condition type. Our results show that OXT increased the perceived pleasantness of female, but not male touch, and associated neural responses in insula, precuneus, orbitofrontal, and pregenual anterior cingulate cortex. Moreover, the behavioral and neural effects of OXT were negatively correlated with autistic-like traits. Taken together, this is the first study to show that the perceived hedonic value of human heterosexual interpersonal touch is facilitated by OXT in men, but that its behavioral and neural effects in this context are blunted in individuals with autistic traits.

  11. Expressive suppression and neural responsiveness to nonverbal affective cues.

    PubMed

    Petrican, Raluca; Rosenbaum, R Shayna; Grady, Cheryl

    2015-10-01

    Optimal social functioning occasionally requires concealment of one's emotions in order to meet one's immediate goals and environmental demands. However, because emotions serve an important communicative function, their habitual suppression disrupts the flow of social exchanges and, thus, incurs significant interpersonal costs. Evidence is accruing that the disruption in social interactions, linked to habitual expressive suppression use, stems not only from intrapersonal, but also from interpersonal causes, since the suppressors' restricted affective displays reportedly inhibit their interlocutors' emotionally expressive behaviors. However, expressive suppression use is not known to lead to clinically significant social impairments. One explanation may be that over the lifespan, individuals who habitually suppress their emotions come to compensate for their interlocutors' restrained expressive behaviors by developing an increased sensitivity to nonverbal affective cues. To probe this issue, the present study used functional magnetic resonance imaging (fMRI) to scan healthy older women while they viewed silent videos of a male social target displaying nonverbal emotional behavior, together with a brief verbal description of the accompanying context, and then judged the target's affect. As predicted, perceivers who reported greater habitual use of expressive suppression showed increased neural processing of nonverbal affective cues. This effect appeared to be coordinated in a top-down manner via cognitive control. Greater neural processing of nonverbal cues among perceivers who habitually suppress their emotions was linked to increased ventral striatum activity, suggestive of increased reward value/personal relevance ascribed to emotionally expressive nonverbal behaviors. These findings thus provide neural evidence broadly consistent with the hypothesized link between habitual use of expressive suppression and compensatory development of increased responsiveness to

  12. Abnormal relationship between GABA, neurophysiology and impulsive behavior in neurofibromatosis type 1.

    PubMed

    Ribeiro, Maria J; Violante, Inês R; Bernardino, Inês; Edden, Richard A E; Castelo-Branco, Miguel

    2015-03-01

    Neurofibromatosis type 1 (NF1) is a neurodevelopmental disorder characterized by a broad spectrum of cognitive deficits. In particular, executive dysfunction is recognized as a core deficit of NF1, including impairments in executive attention and inhibitory control. Yet, the neural mechanisms behind these important deficits are still unknown. Here, we studied inhibitory control in a visual go/no-go task in children and adolescents with NF1 and age- and gender-matched controls (n = 16 per group). We applied a multimodal approach using high-density electroencephalography (EEG), to study the evoked brain responses, and magnetic resonance spectroscopy (MRS) to measure the levels of GABA and glutamate + glutamine in the medial frontal cortex, a brain region that plays a pivotal role in inhibitory control, and also in a control region, the occipital cortex. Finally, we run correlation analyses to identify the relationship between inhibitory control, levels of neurotransmitters, and EEG markers of neural function. Individuals with NF1 showed impaired impulse control and reduced EEG correlates of early visual processing (parieto-occipital P1) and inhibitory control (frontal P3). MRS data revealed a reduction in medial frontal GABA+/tCr (total Creatine) levels in the NF1 group, in parallel with the already reported reduced occipital GABA levels. In contrast, glutamate + glutamine/tCr levels were normal, suggesting the existence of abnormal inhibition/excitation balance in this disorder. Notably, medial frontal but not occipital GABA levels correlated with general intellectual abilities (IQ) in NF1, and inhibitory control in both groups. Surprisingly, the relationship between inhibitory control and medial frontal GABA was reversed in NF1: higher GABA was associated with a faster response style whereas in controls it was related to a cautious strategy. Abnormal GABAergic physiology appears, thus, as an important factor underlying impaired cognition in NF1, in a level and

  13. Exacerbated immune stress response during experimental magnesium deficiency results from abnormal cell calcium homeostasis.

    PubMed

    Malpuech-Brugère, C; Rock, E; Astier, C; Nowacki, W; Mazur, A; Rayssiguier, Y

    1998-01-01

    The aim of this study was to assess the potential mechanism underlying the enhanced inflammatory processes during magnesium deficit. In this study, exacerbated response to live bacteria and platelet activating factors was shown in rats fed a magnesium-deficient diet. Peritoneal cells from these animals also showed enhanced superoxide anion production and calcium mobilising potency following in vitro stimulation. The latter effect occurred very early in the course of magnesium deficiency. These studies first showed that an abnormal calcium handling induced by extracellular magnesium depression in vivo may be at the origin of exacerbated inflammatory response.

  14. Anything goes? Regulation of the neural processes underlying response inhibition in TBI patients.

    PubMed

    Moreno-López, Laura; Manktelow, Anne E; Sahakian, Barbara J; Menon, David K; Stamatakis, Emmanuel A

    2017-02-01

    Despite evidence for beneficial use of methylphenidate in response inhibition, no studies so far have investigated the effects of this drug in the neurobiology of inhibitory control in traumatic brain injury (TBI), even though impulsive behaviours are frequently reported in this patient group. We investigated the neural basis of response inhibition in a group of TBI patients using functional magnetic resonance imaging and a stop-signal paradigm. In a randomised double-blinded crossover study, the patients received either a single 30mg dose of methylphenidate or placebo and performed the stop-signal task. Activation in the right inferior frontal gyrus (RIFG), an area associated with response inhibition, was significantly lower in patients compared to healthy controls. Poor response inhibition in this group was associated with greater connectivity between the RIFG and a set of regions considered to be part of the default mode network (DMN), a finding that suggests the interplay between DMN and frontal executive networks maybe compromised. A single dose of methylphenidate rendered activity and connectivity profiles of the patients RIFG near normal. The results of this study indicate that the neural circuitry involved in response inhibition in TBI patients may be partially restored with methylphenidate. Given the known mechanisms of action of methylphenidate, the effect we observed may be due to increased dopamine and noradrenaline levels. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  15. Evidence of Rapid Modulation by Social Information of Subjective, Physiological, and Neural Responses to Emotional Expressions

    PubMed Central

    Mermillod, Martial; Grynberg, Delphine; Pio-Lopez, Léo; Rychlowska, Magdalena; Beffara, Brice; Harquel, Sylvain; Vermeulen, Nicolas; Niedenthal, Paula M.; Dutheil, Frédéric; Droit-Volet, Sylvie

    2018-01-01

    Recent research suggests that conceptual or emotional factors could influence the perceptual processing of stimuli. In this article, we aimed to evaluate the effect of social information (positive, negative, or no information related to the character of the target) on subjective (perceived and felt valence and arousal), physiological (facial mimicry) as well as on neural (P100 and N170) responses to dynamic emotional facial expressions (EFE) that varied from neutral to one of the six basic emotions. Across three studies, the results showed reduced ratings of valence and arousal of EFE associated with incongruent social information (Study 1), increased electromyographical responses (Study 2), and significant modulation of P100 and N170 components (Study 3) when EFE were associated with social (positive and negative) information (vs. no information). These studies revealed that positive or negative social information reduces subjective responses to incongruent EFE and produces a similar neural and physiological boost of the early perceptual processing of EFE irrespective of their congruency. In conclusion, the article suggests that the presence of positive or negative social context modulates early physiological and neural activity preceding subsequent behavior. PMID:29375330

  16. The neurobiology of abnormal manifestations of aggression--a review of hypothalamic mechanisms in cats, rodents, and humans.

    PubMed

    Haller, Jozsef

    2013-04-01

    Aggression research was for long dominated by the assumption that aggression-related psychopathologies result from the excessive activation of aggression-promoting brain mechanisms. This assumption was recently challenged by findings with models of aggression that mimic etiological factors of aggression-related psychopathologies. Subjects submitted to such procedures show abnormal attack features (mismatch between provocation and response, disregard of species-specific rules, and insensitivity toward the social signals of opponents). We review here 12 such laboratory models and the available human findings on the neural background of abnormal aggression. We focus on the hypothalamus, a region tightly involved in the execution of attacks. Data show that the hypothalamic mechanisms controlling attacks (general activation levels, local serotonin, vasopressin, substance P, glutamate, GABA, and dopamine neurotransmission) undergo etiological factor-dependent changes. Findings suggest that the emotional component of attacks differentiates two basic types of hypothalamic mechanisms. Aggression associated with increased arousal (emotional/reactive aggression) is paralleled by increased mediobasal hypothalamic activation, increased hypothalamic vasopressinergic, but diminished hypothalamic serotonergic neurotransmission. In aggression models associated with low arousal (unemotional/proactive aggression), the lateral but not the mediobasal hypothalamus is over-activated. In addition, the anti-aggressive effect of serotonergic neurotransmission is lost and paradoxical changes were noticed in vasopressinergic neurotransmission. We conclude that there is no single 'neurobiological road' to abnormal aggression: the neural background shows qualitative, etiological factor-dependent differences. Findings obtained with different models should be viewed as alternative mechanisms rather than conflicting data. The relevance of these findings for understanding and treating of aggression

  17. Play It Again: Neural Responses to Reunion with Excluders Predicted by Attachment Patterns

    ERIC Educational Resources Information Center

    White, Lars O.; Wu, Jia; Borelli, Jessica L.; Mayes, Linda C.; Crowley, Michael J.

    2013-01-01

    Reunion behavior following stressful separations from caregivers is often considered the single most sensitive clue to infant attachment patterns. Extending these ideas to middle childhood/early adolescence, we examined participants' neural responses to reunion with peers who had previously excluded them. We recorded event-related potentials…

  18. Associations Among Pubertal Development, Empathic Ability, and Neural Responses While Witnessing Peer Rejection in Adolescence

    PubMed Central

    Masten, Carrie L.; Eisenberger, Naomi I.; Pfeifer, Jennifer H.; Colich, Natalie L.; Dapretto, Mirella

    2012-01-01

    Links among concurrent and longitudinal changes in pubertal development and empathic ability from age 10 to 13 and neural responses while witnessing peer rejection at age 13 were examined in 16 participants. More advanced pubertal development at age 13, and greater longitudinal increases in pubertal development, related to increased activity in regions underlying cognitive aspects of empathy. Likewise, at age 13 greater perspective taking related to activity in cognitive empathy-related regions; however, affective components of empathy (empathic concern and personal distress) were additionally associated with activity in affective pain-related regions. Longitudinal increases in empathic ability related to cognitive and affective empathy-related circuitry. Findings provide preliminary evidence that physical and cognitive-emotional development relate to adolescents’ neural responses when witnessing peer rejection. PMID:23379360

  19. Do Hostile School Environments Promote Social Deviance by Shaping Neural Responses to Social Exclusion?

    PubMed

    Schriber, Roberta A; Rogers, Christina R; Ferrer, Emilio; Conger, Rand D; Robins, Richard W; Hastings, Paul D; Guyer, Amanda E

    2018-03-01

    The present study examined adolescents' neural responses to social exclusion as a mediator of past exposure to a hostile school environment (HSE) and later social deviance, and whether family connectedness buffered these associations. Participants (166 Mexican-origin adolescents, 54.4% female) reported on their HSE exposure and family connectedness across Grades 9-11. Six months later, neural responses to social exclusion were measured. Finally, social deviance was self-reported in Grades 9 and 12. The HSE-social deviance link was mediated by greater reactivity to social deviance in subgenual anterior cingulate cortex, a region from the social pain network also implicated in social susceptibility. However, youths with stronger family bonds were protected from this neurobiologically mediated path. These findings suggest a complex interplay of risk and protective factors that impact adolescent behavior through the brain. © 2018 Society for Research on Adolescence.

  20. Neural source dynamics of brain responses to continuous stimuli: Speech processing from acoustics to comprehension.

    PubMed

    Brodbeck, Christian; Presacco, Alessandro; Simon, Jonathan Z

    2018-05-15

    Human experience often involves continuous sensory information that unfolds over time. This is true in particular for speech comprehension, where continuous acoustic signals are processed over seconds or even minutes. We show that brain responses to such continuous stimuli can be investigated in detail, for magnetoencephalography (MEG) data, by combining linear kernel estimation with minimum norm source localization. Previous research has shown that the requirement to average data over many trials can be overcome by modeling the brain response as a linear convolution of the stimulus and a kernel, or response function, and estimating a kernel that predicts the response from the stimulus. However, such analysis has been typically restricted to sensor space. Here we demonstrate that this analysis can also be performed in neural source space. We first computed distributed minimum norm current source estimates for continuous MEG recordings, and then computed response functions for the current estimate at each source element, using the boosting algorithm with cross-validation. Permutation tests can then assess the significance of individual predictor variables, as well as features of the corresponding spatio-temporal response functions. We demonstrate the viability of this technique by computing spatio-temporal response functions for speech stimuli, using predictor variables reflecting acoustic, lexical and semantic processing. Results indicate that processes related to comprehension of continuous speech can be differentiated anatomically as well as temporally: acoustic information engaged auditory cortex at short latencies, followed by responses over the central sulcus and inferior frontal gyrus, possibly related to somatosensory/motor cortex involvement in speech perception; lexical frequency was associated with a left-lateralized response in auditory cortex and subsequent bilateral frontal activity; and semantic composition was associated with bilateral temporal and

  1. Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

    PubMed

    Oliver, Jason A; Evans, David E; Addicott, Merideth A; Potts, Geoffrey F; Brandon, Thomas H; Drobes, David J

    2017-06-01

    Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p < .001). Exploratory analyses indicated withdrawal increased time to initiate the next trial following unexpected punishment trials (p < .001) and response time on reward trials during withdrawal was positively related to nicotine dependence (p < .001). Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in

  2. Gender Differences in Neural Responses to Perceptually Invisible Fearful Face—An ERP Study

    PubMed Central

    Lee, Seung A.; Kim, Chai-Youn; Shim, Miseon; Lee, Seung-Hwan

    2017-01-01

    Women tend to respond to emotional stimuli differently from men. This study aimed at investigating whether neural responses to perceptually “invisible” emotional stimuli differ between men and women by exploiting event-related potential (ERP). Forty healthy participants (21 women) were recruited for the main experiment. A control experiment was conducted by excluding nine (7 women) participants from the main experiment and replacing them with additional ten (6 women) participants (total 41 participants) where Beck's Anxiety Inventory (BAI) and Beck's Depression Inventory (BDI) scores were controlled. Using the visual backward masking paradigm, either a fearful or a neutral face stimulus was presented in varied durations (subthreshold, near-threshold, or suprathreshold) followed by a mask. Participants performed a two-alternative forced choice (2-AFC) emotion discrimination task on each face. Behavioral analysis showed that participants were unaware of masked stimuli of which duration was the shortest and, therefore, processed at subthreshold. Nevertheless, women showed significantly larger response in P100 amplitude to subthreshold fearful faces than men. This result remained consistent in the control experiment. Our findings indicate gender-differences in neural response to subthreshold emotional face, which is reflected in the early processing stage. PMID:28184189

  3. Bayesian Mapping Reveals That Attention Boosts Neural Responses to Predicted and Unpredicted Stimuli.

    PubMed

    Garrido, Marta I; Rowe, Elise G; Halász, Veronika; Mattingley, Jason B

    2018-05-01

    Predictive coding posits that the human brain continually monitors the environment for regularities and detects inconsistencies. It is unclear, however, what effect attention has on expectation processes, as there have been relatively few studies and the results of these have yielded contradictory findings. Here, we employed Bayesian model comparison to adjudicate between 2 alternative computational models. The "Opposition" model states that attention boosts neural responses equally to predicted and unpredicted stimuli, whereas the "Interaction" model assumes that attentional boosting of neural signals depends on the level of predictability. We designed a novel, audiospatial attention task that orthogonally manipulated attention and prediction by playing oddball sequences in either the attended or unattended ear. We observed sensory prediction error responses, with electroencephalography, across all attentional manipulations. Crucially, posterior probability maps revealed that, overall, the Opposition model better explained scalp and source data, suggesting that attention boosts responses to predicted and unpredicted stimuli equally. Furthermore, Dynamic Causal Modeling showed that these Opposition effects were expressed in plastic changes within the mismatch negativity network. Our findings provide empirical evidence for a computational model of the opposing interplay of attention and expectation in the brain.

  4. Prediction of forced expiratory volume in pulmonary function test using radial basis neural networks and k-means clustering.

    PubMed

    Manoharan, Sujatha C; Ramakrishnan, Swaminathan

    2009-10-01

    In this work, prediction of forced expiratory volume in pulmonary function test, carried out using spirometry and neural networks is presented. The pulmonary function data were recorded from volunteers using commercial available flow volume spirometer in standard acquisition protocol. The Radial Basis Function neural networks were used to predict forced expiratory volume in 1 s (FEV1) from the recorded flow volume curves. The optimal centres of the hidden layer of radial basis function were determined by k-means clustering algorithm. The performance of the neural network model was evaluated by computing their prediction error statistics of average value, standard deviation, root mean square and their correlation with the true data for normal, restrictive and obstructive cases. Results show that the adopted neural networks are capable of predicting FEV1 in both normal and abnormal cases. Prediction accuracy was more in obstructive abnormality when compared to restrictive cases. It appears that this method of assessment is useful in diagnosing the pulmonary abnormalities with incomplete data and data with poor recording.

  5. Postpartum depressive symptoms moderate the link between mothers’ neural response to positive faces in reward and social regions and observed caregiving

    PubMed Central

    Guo, Chaohui; Moses-Kolko, Eydie L; Phillips, Mary L; Stepp, Stephanie D; Hipwell, Alison E

    2017-01-01

    Abstract Postpartum depression may disrupt socio-affective neural circuitry and compromise provision of positive parenting. Although work has evaluated how parental response to negative stimuli is related to caregiving, research is needed to examine how depressive symptoms during the postpartum period may be related to neural response to positive stimuli, especially positive faces, given depression’s association with biased processing of positive faces. The current study examined the association between neural response to adult happy faces and observations of maternal caregiving and the moderating role of postpartum depression, in a sample of 18- to 22-year old mothers (n = 70) assessed at 17 weeks (s.d. = 4.7 weeks) postpartum. Positive caregiving was associated with greater precuneus and occipital response to positive faces among mothers with lower depressive symptoms, but not for those with higher symptoms. For mothers with higher depressive symptoms, greater ventral and dorsal striatal response to positive faces was associated with more positive caregiving, whereas the opposite pattern emerged for mothers with lower symptoms. There was no association between negative caregiving and neural response to positive faces or negative faces. Processing of positive stimuli may be an important prognostic target in mothers with depressive symptoms, given its link with healthy caregiving behaviors. PMID:29048603

  6. Cumulative Adversity Sensitizes Neural Response to Acute Stress: Association with Health Symptoms

    PubMed Central

    Seo, Dongju; Tsou, Kristen A; Ansell, Emily B; Potenza, Marc N; Sinha, Rajita

    2014-01-01

    Cumulative adversity (CA) increases stress sensitivity and risk of adverse health outcomes. However, neural mechanisms underlying these associations in humans remain unclear. To understand neural responses underlying the link between CA and adverse health symptoms, the current study assessed brain activity during stress and neutral-relaxing states in 75 demographically matched, healthy individuals with high, mid, and low CA (25 in each group), and their health symptoms using the Cornell Medical Index. CA was significantly associated with greater adverse health symptoms (P=0.01) in all participants. Functional magnetic resonance imaging results indicated significant associations between CA scores and increased stress-induced activity in the lateral prefrontal cortex, insula, striatum, right amygdala, hippocampus, and temporal regions in all 75 participants (p<0.05, whole-brain corrected). In addition to these regions, the high vs low CA group comparison revealed decreased stress-induced activity in the medial orbitofrontal cortex (OFC) in the high CA group (p<0.01, whole-brain corrected). Specifically, hypoactive medial OFC and hyperactive right hippocampus responses to stress were each significantly associated with greater adverse health symptoms (p<0.01). Furthermore, an inverse correlation was found between activity in the medial OFC and right hippocampus (p=0.01). These results indicate that high CA sensitizes limbic–striatal responses to acute stress and also identifies an important role for stress-related medial OFC and hippocampus responses in the effects of CA on increasing vulnerability to adverse health consequences. PMID:24051900

  7. Cumulative adversity sensitizes neural response to acute stress: association with health symptoms.

    PubMed

    Seo, Dongju; Tsou, Kristen A; Ansell, Emily B; Potenza, Marc N; Sinha, Rajita

    2014-02-01

    Cumulative adversity (CA) increases stress sensitivity and risk of adverse health outcomes. However, neural mechanisms underlying these associations in humans remain unclear. To understand neural responses underlying the link between CA and adverse health symptoms, the current study assessed brain activity during stress and neutral-relaxing states in 75 demographically matched, healthy individuals with high, mid, and low CA (25 in each group), and their health symptoms using the Cornell Medical Index. CA was significantly associated with greater adverse health symptoms (P=0.01) in all participants. Functional magnetic resonance imaging results indicated significant associations between CA scores and increased stress-induced activity in the lateral prefrontal cortex, insula, striatum, right amygdala, hippocampus, and temporal regions in all 75 participants (p<0.05, whole-brain corrected). In addition to these regions, the high vs low CA group comparison revealed decreased stress-induced activity in the medial orbitofrontal cortex (OFC) in the high CA group (p<0.01, whole-brain corrected). Specifically, hypoactive medial OFC and hyperactive right hippocampus responses to stress were each significantly associated with greater adverse health symptoms (p<0.01). Furthermore, an inverse correlation was found between activity in the medial OFC and right hippocampus (p=0.01). These results indicate that high CA sensitizes limbic-striatal responses to acute stress and also identifies an important role for stress-related medial OFC and hippocampus responses in the effects of CA on increasing vulnerability to adverse health consequences.

  8. Individual Differences in Risk Preference Predict Neural Responses during Financial Decision-Making

    PubMed Central

    Engelmann, Jan B.; Tamir, Diana

    2009-01-01

    We investigated the neural correlates of subjective valuations during a task involving risky choices about lotteries. Because expected value was held constant across all lotteries, decisions were influenced by subjective preferences, which manifest behaviorally as risk-seeking or risk-averse attitudes. To isolate structures encoding risk preference during choice, we probed for areas showing increased activation as a function of selected risk-level. Such response patterns were obtained in anterior (ACC) and posterior cingulate cortex (PCC), superior frontal gyrus, caudate nucleus, and substantia nigra. Behavioral results revealed the presence of risk-averse and risk-neutral individuals. In parallel, brain signals revealed modulation of activity by risk-attitude during choice. Correlations between risk-seeking attitudes and neural activity during risky choice were obtained in superior and inferior frontal gyri, medial and lateral orbitofrontal cortex, and parahippocampal gyrus, while correlations with risk-averse attitudes were found in the caudate. The dynamics of neural responses relevant to each stage of the task (decision, anticipation, outcome) were investigated via timeseries and conjunction analyses. Though the networks engaged in each of the task stages were mostly distinct, regions of ACC, PCC and caudate were consistently activated during each decision-making phase. These results demonstrate (1) that subjective assessments of risk, as well as individual attitudes toward risk, play a significant role in modulating activity within brain regions recruited during decision-making, and (2) that ACC, PCC and caudate are relevant during each phase of a decision-making task requiring subjective valuations, strengthening the role of these regions in self-referential subjective valuations during choice. PMID:19576868

  9. Neural patterning of human induced pluripotent stem cells in 3-D cultures for studying biomolecule-directed differential cellular responses.

    PubMed

    Yan, Yuanwei; Bejoy, Julie; Xia, Junfei; Guan, Jingjiao; Zhou, Yi; Li, Yan

    2016-09-15

    Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells/tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capacity of signaling factors that regulate 3-D neural tissue patterning in vitro and differential responses of the resulting neural populations to various biomolecules have not yet been fully understood. By tuning neural patterning of hiPSCs with small molecules targeting sonic hedgehog (SHH) signaling, this study generated different 3-D neuronal cultures that were mainly comprised of either cortical glutamatergic neurons or motor neurons. Abundant glutamatergic neurons were observed following the treatment with an antagonist of SHH signaling, cyclopamine, while Islet-1 and HB9-expressing motor neurons were enriched by an SHH agonist, purmorphamine. In neurons derived with different neural patterning factors, whole-cell patch clamp recordings showed similar voltage-gated Na(+)/K(+) currents, depolarization-evoked action potentials and spontaneous excitatory post-synaptic currents. Moreover, these different neuronal populations exhibited differential responses to three classes of biomolecules, including (1) matrix metalloproteinase inhibitors that affect extracellular matrix remodeling; (2) N-methyl-d-aspartate that induces general neurotoxicity; and (3) amyloid β (1-42) oligomers that cause neuronal subtype-specific neurotoxicity. This study should advance our understanding of hiPSC self-organization and neural tissue development and provide a transformative approach to establish 3-D models for neurological disease modeling and drug discovery. Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells, tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capability of sonic hedgehog-related small molecules to tune

  10. Epigenetic regulation of the oxytocin receptor is associated with neural response during selective social attention.

    PubMed

    Puglia, Meghan H; Connelly, Jessica J; Morris, James P

    2018-06-15

    Aberrant attentional biases to social stimuli have been implicated in a number of disorders including autism and social anxiety disorder. Oxytocin, a naturally-occurring mammalian hormone and neuromodulator involved in regulating social behavior, has been proposed to impact basic biological systems that facilitate the detection of and orientation to social information. Here, we investigate a role for naturally-occurring variability in the endogenous oxytocinergic system in regulating neural response during attention to social information. Participants performed a selective social attention task while undergoing fMRI, provided a blood sample for epigenetic analysis, and completed self-report measures of social functioning. We find that a functional epigenetic modification to the oxytocin receptor, OXTR methylation, is associated with increased neural response within and decreased functional coupling between regions of the salience and attentional control networks during selective social attention. We also show that subclinical variability in autistic and social anxiety traits moderates this epigenetic regulation of neural response. These data offer a mechanistic explanation to a growing literature associating social behavior and disorder with epigenetic modification to OXTR by suggesting that OXTR methylation reflects a decrease in the extent to which social information automatically captures attention. We highlight the importance that treatment efficacy be considered in relation to individual differences in molecular makeup, and that future studies aimed at uncovering biomarkers of disorder carefully consider measurement at both the biological and phenotypic level.

  11. Viscoelastic response of neural cells governed by the deposition of amyloid-β peptides (Aβ)

    NASA Astrophysics Data System (ADS)

    Gong, Ze; You, Ran; Chang, Raymond Chuen-Chung; Lin, Yuan

    2016-06-01

    Because of its intimate relation with Alzheimer's disease (AD), the question of how amyloid-β peptide (Aβ) deposition alters the membrane and cytoskeltal structure of neural cells and eventually their mechanical response has received great attention. In this study, the viscoelastic properties of primary neurons subjected to various Aβ treatments were systematically characterized using atomic force microrheology. It was found that both the storage ( G ') and loss ( G ″) moduli of neural cells are rate-dependent and grow by orders of magnitude as the driving frequency ω varies from 1 to 100 Hz. However, a much stronger frequency dependence was observed in the loss moduli (with a scaling exponent of ˜0.96) than that in G ' ( ˜ ω 0.2 ). Furthermore, both cell moduli increase gradually within the first 6 h of Aβ treatment before steady-state values are reached, with a higher dosage of Aβ leading to larger changes in cell properties. Interestingly, we showed that the measured neuron response can be well-explained by a power law structural damping model. Findings here establish a quantitative link between Aβ accumulation and the physical characteristics of neural cells and hence could provide new insights into how disorders like AD affect the progression of different neurological processes from a mechanics point of view.

  12. The Neural Basis of Responsibility Attribution in Decision-Making

    PubMed Central

    Li, Peng; Shen, Yue; Sui, Xue; Chen, Changming; Feng, Tingyong; Li, Hong; Holroyd, Clay

    2013-01-01

    Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent’s emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context. PMID:24224053

  13. Three-Dimensional Flexible Electronics Enabled by Shape Memory Polymer Substrates for Responsive Neural Interfaces.

    PubMed

    Ware, Taylor; Simon, Dustin; Hearon, Keith; Liu, Clive; Shah, Sagar; Reeder, Jonathan; Khodaparast, Navid; Kilgard, Michael P; Maitland, Duncan J; Rennaker, Robert L; Voit, Walter E

    2012-12-01

    Planar electronics processing methods have enabled neural interfaces to become more precise and deliver more information. However, this processing paradigm is inherently 2D and rigid. The resulting mechanical and geometrical mismatch at the biotic-abiotic interface can elicit an immune response that prevents effective stimulation. In this work, a thiol-ene/acrylate shape memory polymer is utilized to create 3D softening substrates for stimulation electrodes. This substrate system is shown to soften in vivo from more than 600 to 6 MPa. A nerve cuff electrode that coils around the vagus nerve in a rat and that drives neural activity is demonstrated.

  14. Neural autonomic control in orthostatic intolerance.

    PubMed

    Furlan, Raffaello; Barbic, Franca; Casella, Francesco; Severgnini, Giorgio; Zenoni, Luca; Mercieri, Angelo; Mangili, Ruggero; Costantino, Giorgio; Porta, Alberto

    2009-10-01

    Inability to maintain the upright position is manifested by a number of symptoms shared by either human pathophysiology and conditions following weightlessness or bed rest. Alterations of the neural sympathetic cardiovascular control have been suggested to be one of the potential underlying etiopathogenetic mechanisms in these conditions. We hypothesize that the study of the autonomic profile of human orthostatic intolerance syndromes may furnish a valuable insight into the complexity of the sympathetic alterations leading to a reduced gravitational tolerance. In the present paper we describe abnormalities both in the magnitude and in the pattern of the sympathetic neural firing observed in patients affected by orthostatic intolerance, attending the upright position. Also, we discuss similarity and differences in the neural sympathetic mechanisms regulating the cardiovascular system during the gravitational stimulus both in clinical syndromes and in subjects returning from space.

  15. Neural responses in songbird forebrain reflect learning rates, acquired salience, and stimulus novelty after auditory discrimination training.

    PubMed

    Bell, Brittany A; Phan, Mimi L; Vicario, David S

    2015-03-01

    How do social interactions form and modulate the neural representations of specific complex signals? This question can be addressed in the songbird auditory system. Like humans, songbirds learn to vocalize by imitating tutors heard during development. These learned vocalizations are important in reproductive and social interactions and in individual recognition. As a model for the social reinforcement of particular songs, male zebra finches were trained to peck for a food reward in response to one song stimulus (GO) and to withhold responding for another (NoGO). After performance reached criterion, single and multiunit neural responses to both trained and novel stimuli were obtained from multiple electrodes inserted bilaterally into two songbird auditory processing areas [caudomedial mesopallium (CMM) and caudomedial nidopallium (NCM)] of awake, restrained birds. Neurons in these areas undergo stimulus-specific adaptation to repeated song stimuli, and responses to familiar stimuli adapt more slowly than to novel stimuli. The results show that auditory responses differed in NCM and CMM for trained (GO and NoGO) stimuli vs. novel song stimuli. When subjects were grouped by the number of training days required to reach criterion, fast learners showed larger neural responses and faster stimulus-specific adaptation to all stimuli than slow learners in both areas. Furthermore, responses in NCM of fast learners were more strongly left-lateralized than in slow learners. Thus auditory responses in these sensory areas not only encode stimulus familiarity, but also reflect behavioral reinforcement in our paradigm, and can potentially be modulated by social interactions. Copyright © 2015 the American Physiological Society.

  16. Neural crest stem cell multipotency requires Foxd3 to maintain neural potential and repress mesenchymal fates.

    PubMed

    Mundell, Nathan A; Labosky, Patricia A

    2011-02-01

    Neural crest (NC) progenitors generate a wide array of cell types, yet molecules controlling NC multipotency and self-renewal and factors mediating cell-intrinsic distinctions between multipotent versus fate-restricted progenitors are poorly understood. Our earlier work demonstrated that Foxd3 is required for maintenance of NC progenitors in the embryo. Here, we show that Foxd3 mediates a fate restriction choice for multipotent NC progenitors with loss of Foxd3 biasing NC toward a mesenchymal fate. Neural derivatives of NC were lost in Foxd3 mutant mouse embryos, whereas abnormally fated NC-derived vascular smooth muscle cells were ectopically located in the aorta. Cranial NC defects were associated with precocious differentiation towards osteoblast and chondrocyte cell fates, and individual mutant NC from different anteroposterior regions underwent fate changes, losing neural and increasing myofibroblast potential. Our results demonstrate that neural potential can be separated from NC multipotency by the action of a single gene, and establish novel parallels between NC and other progenitor populations that depend on this functionally conserved stem cell protein to regulate self-renewal and multipotency.

  17. Protease-degradable PEG-maleimide coating with on-demand release of IL-1Ra to improve tissue response to neural electrodes

    PubMed Central

    Gutowski, Stacie M.; Shoemaker, James T.; Templeman, Kellie L.; Wei, Yang; Latour, Robert A.; Bellamkonda, Ravi V.; LaPlaca, Michelle C.; García, Andrés J.

    2015-01-01

    Neural electrodes are an important part of brain-machine interface devices that can restore functionality to patients with sensory and movement disorders. Chronically implanted neural electrodes induce an unfavorable tissue response which includes inflammation, scar formation, and neuronal cell death, eventually causing loss of electrode function. We developed a poly(ethylene glycol) hydrogel coating for neural electrodes with non-fouling characteristics, incorporated an anti-inflammatory agent, and engineered a stimulus-responsive degradable portion for on-demand release of the anti-inflammatory agent in response to inflammatory stimuli. This coating reduces in vitro glial cell adhesion, cell spreading, and cytokine release compared to uncoated controls. We also analyzed the in vivo tissue response using immunohistochemistry and microarray qRT-PCR. Although no differences were observed among coated and uncoated electrodes for inflammatory cell markers, lower IgG penetration into the tissue around PEG+IL-1Ra coated electrodes indicates an improvement in blood-brain barrier integrity. Gene expression analysis showed higher expression of IL-6 and MMP-2 around PEG+IL-1Ra samples, as well as an increase in CNTF expression, an important marker for neuronal survival. Importantly, increased neuronal survival around coated electrodes compared to uncoated controls was observed. Collectively, these results indicate promising findings for an engineered coating to increase neuronal survival and improve tissue response around implanted neural electrodes. PMID:25617126

  18. Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P.

    PubMed

    Guagnini, F; Valenti, M; Mukenge, S; Matias, I; Bianchetti, A; Di Palo, S; Ferla, G; Di Marzo, V; Croci, T

    2006-07-01

    Diverticulosis is a common disease of not completely defined pathogenesis. Motor abnormalities of the intestinal wall have been frequently described but very little is known about their mechanisms. We investigated in vitro the neural response of colonic longitudinal muscle strips from patients undergoing surgery for complicated diverticular disease (diverticulitis). The neural contractile response to electrical field stimulation of longitudinal muscle strips from the colon of patients undergoing surgery for colonic cancer or diverticulitis was challenged by different receptor agonists and antagonists. Contractions of colonic strips from healthy controls and diverticulitis specimens were abolished by atropine. The beta adrenergic agonist (-) isoprenaline and the tachykinin NK1 receptor antagonist SR140333 had similar potency in reducing the electrical twitch response in controls and diseased tissues, while the cannabinoid receptor agonist (+)WIN 55,212-2 was 100 times more potent in inhibiting contractions in controls (IC50 42 nmol/l) than in diverticulitis strips. SR141716, a selective antagonist of the cannabinoid CB1 receptor, had no intrinsic activity in control preparations but potentiated the neural twitch in diseased tissues by up to 196% in a concentration dependent manner. SR141716 inhibited (+)WIN 55,212-2 induced relaxation in control strips but had no efficacy on (+)WIN 55,212-2 responses in strips from diverticular disease patients. Colonic levels of the endogenous ligand of cannabinoid and vanilloid TRPV1 receptors anandamide were more than twice those of control tissues (54 v 27 pmol/g tissue). The axonal conduction blocker tetrodotoxin had opposite effects in the two preparations, completely inhibiting the contractions of control strips but potentiating those in diverticular preparations, an effect selectively inhibited by SR140333. Neural control of colon motility is profoundly altered in patients with diverticulitis. Their raised levels of

  19. The morphological classification of normal and abnormal red blood cell using Self Organizing Map

    NASA Astrophysics Data System (ADS)

    Rahmat, R. F.; Wulandari, F. S.; Faza, S.; Muchtar, M. A.; Siregar, I.

    2018-02-01

    Blood is an essential component of living creatures in the vascular space. For possible disease identification, it can be tested through a blood test, one of which can be seen from the form of red blood cells. The normal and abnormal morphology of the red blood cells of a patient is very helpful to doctors in detecting a disease. With the advancement of digital image processing technology can be used to identify normal and abnormal blood cells of a patient. This research used self-organizing map method to classify the normal and abnormal form of red blood cells in the digital image. The use of self-organizing map neural network method can be implemented to classify the normal and abnormal form of red blood cells in the input image with 93,78% accuracy testing.

  20. Gender Differences in Behavioral and Neural Responses to Unfairness Under Social Pressure.

    PubMed

    Zheng, Li; Ning, Reipeng; Li, Lin; Wei, Chunli; Cheng, Xuemei; Zhou, Chu; Guo, Xiuyan

    2017-10-18

    Numerous studies have revealed the key role of social pressure on individuals' decision-making processes. However, the impact of social pressure on unfairness-related decision-making processes remains unclear. In the present study, we investigated how social pressure modulated men's and women's responses in an ultimatum game. Twenty women and eighteen men played the ultimatum game as responders in the scanner, where fair and unfair offers were tendered by proposers acting alone (low pressure) or by proposers endorsed by three supporters (high pressure). Results showed that men rejected more, whereas women accepted more unfair offers in the high versus low pressure context. Neurally, pregenual anterior cingulate cortex activation in women positively predicted their acceptance rate difference between contexts. In men, stronger right anterior insula activation and increased connectivity between right anterior insula and dorsal anterior cingulate cortex were observed when they receiving unfair offers in the high than low pressure context. Furthermore, more bilateral anterior insula and left dorsolateral prefrontal cortex activations were found when men rejected (relative to accepted) unfair offers in the high than low pressure context. These findings highlighted gender differences in the modulation of behavioral and neural responses to unfairness by social pressure.

  1. Racial bias in neural response to others' pain is reduced with other-race contact.

    PubMed

    Cao, Yuan; Contreras-Huerta, Luis Sebastian; McFadyen, Jessica; Cunnington, Ross

    2015-09-01

    Observing the pain of others has been shown to elicit greater activation in sensory and emotional areas of the brain suggested to represent a neural marker of empathy. This modulation of brain responses to others' pain is dependent on the race of the observed person, such that observing own-race people in pain is associated with greater activity in the anterior cingulate and bilateral insula cortices compared to other-race people. Importantly, it is not known how this racial bias to pain in other-race individuals might change over time in new immigrants or might depend on the level and quality of contact with people of the other-race. We investigated these issues by recruiting Chinese students who had first arrived in Australia within the past 6 months to 5 years and assessing their level of contact with other races across different social contexts using comprehensive rating scales. During fMRI, participants observed videos of own-race/other-race individuals, as well as own-group/other-group individuals, receiving painful or non-painful touch. The typical racial bias in neural responses to observed pain was evident, whereby activation in the anterior cingulate cortex (ACC) was greater for pain in own-race compared to other-race people. Crucially, activation in the anterior cingulate to pain in other races increased significantly with the level of contact participants reported with people of the other race. Importantly, this correlation did not depend on the closeness of contact or personal relationships, but simply on the overall level of experience with people of the other race in their every-day environment. Racial bias in neural responses to others' pain, as a neural marker of empathy, therefore changes with experience in new immigrants at least within 5 years of arrival in the new society and, crucially, depends on the level of contact with people of the other race in every-day life contexts. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights

  2. Beauty is in the belief of the beholder: cognitive influences on the neural response to facial attractiveness

    PubMed Central

    Thiruchselvam, Ravi; Harper, Jessica; Homer, Abigail L.

    2016-01-01

    Judgments of facial attractiveness are central to decision-making in various domains, but little is known about the extent to which they are malleable. In this study, we used EEG/ERP methods to examine two novel influences on neural and subjective responses to facial attractiveness: an observer’s expectation and repetition. In each trial of our task, participants viewed either an ordinary or attractive face. To alter expectations, the faces were preceded by a peer-rating that ostensibly reflected the overall attractiveness value assigned to that face by other individuals. To examine the impact of repetition, trials were presented twice throughout the experimental session. Results showed that participants’ expectations about a person’s attractiveness level powerfully altered both the neural response (i.e. the late positive potential; LPP) and self-reported attractiveness ratings. Intriguingly, repetition enhanced both the LPP and self-reported attractiveness as well. Exploratory analyses further suggested that both observer expectation and repetition modulated early neural responses (i.e. the early posterior negativity; EPN) elicited by facial attractiveness. Collectively, these results highlight novel influences on a core social judgment that underlies individuals’ affective lives. PMID:27522090

  3. Neural Responses to Peer Rejection in Anxious Adolescents: Contributions from the Amygdala-Hippocampal Complex

    ERIC Educational Resources Information Center

    Lau, Jennifer Y. F.; Guyer, Amanda E.; Tone, Erin B.; Jenness, Jessica; Parrish, Jessica M.; Pine, Daniel S.; Nelson, Eric E.

    2012-01-01

    Peer rejection powerfully predicts adolescent anxiety. While cognitive differences influence anxious responses to social feedback, little is known about neural contributions. Twelve anxious and twelve age-, gender- and IQ-matched, psychiatrically healthy adolescents received "not interested" and "interested" feedback from unknown peers during a…

  4. Neural network application to comprehensive engine diagnostics

    NASA Technical Reports Server (NTRS)

    Marko, Kenneth A.

    1994-01-01

    We have previously reported on the use of neural networks for detection and identification of faults in complex microprocessor controlled powertrain systems. The data analyzed in those studies consisted of the full spectrum of signals passing between the engine and the real-time microprocessor controller. The specific task of the classification system was to classify system operation as nominal or abnormal and to identify the fault present. The primary concern in earlier work was the identification of faults, in sensors or actuators in the powertrain system as it was exercised over its full operating range. The use of data from a variety of sources, each contributing some potentially useful information to the classification task, is commonly referred to as sensor fusion and typifies the type of problems successfully addressed using neural networks. In this work we explore the application of neural networks to a different diagnostic problem, the diagnosis of faults in newly manufactured engines and the utility of neural networks for process control.

  5. Variability of Neuronal Responses: Types and Functional Significance in Neuroplasticity and Neural Darwinism

    PubMed Central

    Chervyakov, Alexander V.; Sinitsyn, Dmitry O.; Piradov, Michael A.

    2016-01-01

    HIGHLIGHTS We suggest classifying variability of neuronal responses as follows: false (associated with a lack of knowledge about the influential factors), “genuine harmful” (noise), “genuine neutral” (synonyms, repeats), and “genuine useful” (the basis of neuroplasticity and learning).The genuine neutral variability is considered in terms of the phenomenon of degeneracy.Of particular importance is the genuine useful variability that is considered as a potential basis for neuroplasticity and learning. This type of variability is considered in terms of the neural Darwinism theory. In many cases, neural signals detected under the same external experimental conditions significantly change from trial to trial. The variability phenomenon, which complicates extraction of reproducible results and is ignored in many studies by averaging, has attracted attention of researchers in recent years. In this paper, we classify possible types of variability based on its functional significance and describe features of each type. We describe the key adaptive significance of variability at the neural network level and the degeneracy phenomenon that may be important for learning processes in connection with the principle of neuronal group selection. PMID:27932969

  6. Variability of Neuronal Responses: Types and Functional Significance in Neuroplasticity and Neural Darwinism.

    PubMed

    Chervyakov, Alexander V; Sinitsyn, Dmitry O; Piradov, Michael A

    2016-01-01

    HIGHLIGHTS We suggest classifying variability of neuronal responses as follows: false (associated with a lack of knowledge about the influential factors), "genuine harmful" (noise), "genuine neutral" (synonyms, repeats), and "genuine useful" (the basis of neuroplasticity and learning).The genuine neutral variability is considered in terms of the phenomenon of degeneracy.Of particular importance is the genuine useful variability that is considered as a potential basis for neuroplasticity and learning. This type of variability is considered in terms of the neural Darwinism theory. In many cases, neural signals detected under the same external experimental conditions significantly change from trial to trial. The variability phenomenon, which complicates extraction of reproducible results and is ignored in many studies by averaging, has attracted attention of researchers in recent years. In this paper, we classify possible types of variability based on its functional significance and describe features of each type. We describe the key adaptive significance of variability at the neural network level and the degeneracy phenomenon that may be important for learning processes in connection with the principle of neuronal group selection.

  7. Serotonin, neural markers, and memory

    PubMed Central

    Meneses, Alfredo

    2015-01-01

    Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals' species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors as well as SERT (serotonin transporter) seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence. PMID:26257650

  8. Evolution of behavior and neural control of the fast-start escape response.

    PubMed

    Hale, Melina E; Long, John H; McHenry, Matthew J; Westneat, Mark W

    2002-05-01

    The fast-start startle behavior is the primary mechanism of rapid escape in fishes and is a model system for examining neural circuit design and musculoskeletal function. To develop a dataset for evolutionary analysis of the startle response, the kinematics and muscle activity patterns of the fast-start were analyzed for four fish species at key branches in the phylogeny of vertebrates. Three of these species (Polypterus palmas, Lepisosteus osseus, and Amia calva) represent the base of the actinopterygian radiation. A fourth species (Oncorhynchus mykiss) provided data for a species in the central region of the teleost phylogeny. Using these data, we explored the evolution of this behavior within the phylogeny of vertebrates. To test the hypothesis that startle features are evolutionarily conservative, the variability of motor patterns and kinematics in fast-starts was described. Results show that the evolution of the startle behavior in fishes, and more broadly among vertebrates, is not conservative. The fast-start has undergone substantial change in suites of kinematics and electromyogram features, including the presence of either a one- or a two-stage kinematic response and change in the extent of bilateral muscle activity. Comparative methods were used to test the evolutionary hypothesis that changes in motor control are correlated with key differences in the kinematics and behavior of the fast-start. Significant evolutionary correlations were found between several motor pattern and behavioral characters. These results suggest that the startle neural circuit itself is not conservative. By tracing the evolution of motor pattern and kinematics on a phylogeny, it is shown that major changes in the neural circuit of the startle behavior occur at several levels in the phylogeny of vertebrates.

  9. Abnormal Barrier Function in Gastrointestinal Disorders.

    PubMed

    Farré, Ricard; Vicario, María

    2017-01-01

    There is increasing concern in identifying the mechanisms underlying the intimate control of the intestinal barrier, as deregulation of its function is strongly associated with digestive (organic and functional) and a number of non-digestive (schizophrenia, diabetes, sepsis, among others) disorders. The intestinal barrier is a complex and effective defensive functional system that operates to limit luminal antigen access to the internal milieu while maintaining nutrient and electrolyte absorption. Intestinal permeability to substances is mainly determined by the physicochemical properties of the barrier, with the epithelium, mucosal immunity, and neural activity playing a major role. In functional gastrointestinal disorders (FGIDs), the absence of structural or biochemical abnormalities that explain chronic symptoms is probably close to its end, as recent research is providing evidence of structural gut alterations, at least in certain subsets, mainly in functional dyspepsia (FD) and irritable bowel syndrome (IBS). These alterations are associated with increased permeability, which seems to reflect mucosal inflammation and neural activation. The participation of each anatomical and functional component of barrier function in homeostasis and intestinal dysfunction is described, with a special focus on FGIDs.

  10. Abnormal cardiac response to exercise in a murine model of familial hypertrophic cardiomyopathy.

    PubMed

    Nguyen, Lan; Chung, Jessica; Lam, Lien; Tsoutsman, Tatiana; Semsarian, Christopher

    2007-07-10

    Clinical outcome in familial hypertrophic cardiomyopathy (FHC) may be influenced by modifying factors such as exercise. Transgenic mice which overexpress the human disease-causing cTnI gene mutation, Gly203Ser (designated cTnI-G203S), develop all the characteristic phenotypic features of FHC. To study the modifying effect of exercise in early disease, mice underwent swimming exercise at an early age prior to the development of the FHC phenotype. In non-transgenic and cTnI-wt mice, swimming resulted in a significant increase in left ventricular wall thickness and contractility on echocardiography, consistent with a physiological hypertrophic response to exercise. In contrast, cTnI-G203S mice showed no increase in these parameters, indicating an abnormal response to exercise. The lack of a physiological response to exercise may indicate an important novel mechanistic insight into the role of exercise in triggering adverse events in FHC.

  11. Enteric nervous system abnormalities are present in human necrotizing enterocolitis: potential neurotransplantation therapy

    PubMed Central

    2013-01-01

    Introduction Intestinal dysmotility following human necrotizing enterocolitis suggests that the enteric nervous system is injured during the disease. We examined human intestinal specimens to characterize the enteric nervous system injury that occurs in necrotizing enterocolitis, and then used an animal model of experimental necrotizing enterocolitis to determine whether transplantation of neural stem cells can protect the enteric nervous system from injury. Methods Human intestinal specimens resected from patients with necrotizing enterocolitis (n = 18), from control patients with bowel atresia (n = 8), and from necrotizing enterocolitis and control patients undergoing stoma closure several months later (n = 14 and n = 6 respectively) were subjected to histologic examination, immunohistochemistry, and real-time reverse-transcription polymerase chain reaction to examine the myenteric plexus structure and neurotransmitter expression. In addition, experimental necrotizing enterocolitis was induced in newborn rat pups and neurotransplantation was performed by administration of fluorescently labeled neural stem cells, with subsequent visualization of transplanted cells and determination of intestinal integrity and intestinal motility. Results There was significant enteric nervous system damage with increased enteric nervous system apoptosis, and decreased neuronal nitric oxide synthase expression in myenteric ganglia from human intestine resected for necrotizing enterocolitis compared with control intestine. Structural and functional abnormalities persisted months later at the time of stoma closure. Similar abnormalities were identified in rat pups exposed to experimental necrotizing enterocolitis. Pups receiving neural stem cell transplantation had improved enteric nervous system and intestinal integrity, differentiation of transplanted neural stem cells into functional neurons, significantly improved intestinal transit, and significantly decreased

  12. A Point-process Response Model for Spike Trains from Single Neurons in Neural Circuits under Optogenetic Stimulation

    PubMed Central

    Luo, X.; Gee, S.; Sohal, V.; Small, D.

    2015-01-01

    Optogenetics is a new tool to study neuronal circuits that have been genetically modified to allow stimulation by flashes of light. We study recordings from single neurons within neural circuits under optogenetic stimulation. The data from these experiments present a statistical challenge of modeling a high frequency point process (neuronal spikes) while the input is another high frequency point process (light flashes). We further develop a generalized linear model approach to model the relationships between two point processes, employing additive point-process response functions. The resulting model, Point-process Responses for Optogenetics (PRO), provides explicit nonlinear transformations to link the input point process with the output one. Such response functions may provide important and interpretable scientific insights into the properties of the biophysical process that governs neural spiking in response to optogenetic stimulation. We validate and compare the PRO model using a real dataset and simulations, and our model yields a superior area-under-the- curve value as high as 93% for predicting every future spike. For our experiment on the recurrent layer V circuit in the prefrontal cortex, the PRO model provides evidence that neurons integrate their inputs in a sophisticated manner. Another use of the model is that it enables understanding how neural circuits are altered under various disease conditions and/or experimental conditions by comparing the PRO parameters. PMID:26411923

  13. Neural Network Model Of The PXIE RFQ Cooling System and Resonant Frequency Response

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Edelen, Auralee; Biedron, Sandra; Bowring, Daniel

    2016-06-01

    As part of the PIP-II Injector Experiment (PXIE) accel-erator, a four-vane radio frequency quadrupole (RFQ) accelerates a 30-keV, 1-mA to 10-mA H' ion beam to 2.1 MeV. It is designed to operate at a frequency of 162.5 MHz with arbitrary duty factor, including continuous wave (CW) mode. The resonant frequency is controlled solely by a water-cooling system. We present an initial neural network model of the RFQ frequency response to changes in the cooling system and RF power conditions during pulsed operation. A neural network model will be used in a model predictive control scheme to regulate the resonant frequencymore » of the RFQ.« less

  14. Abnormal object recall and anterior cingulate overactivation correlate with formal thought disorder in schizophrenia.

    PubMed

    Assaf, Michal; Rivkin, Paul R; Kuzu, Cheedem H; Calhoun, Vince D; Kraut, Michael A; Groth, Karyn M; Yassa, Michael A; Hart, John; Pearlson, Godfrey D

    2006-03-01

    The neural basis of formal thought disorder (FTD) is unknown. An influential theory is that FTD results from impaired semantic memory processing. We explored the neural correlates of semantic memory retrieval in schizophrenia using an imaging task assessing semantic object recall. Sixteen healthy control subjects and sixteen schizophrenia patients whose FTD symptoms were measured with the Thought Disorder Index completed a verbal object-recall task during functional magnetic resonance imaging. Participants viewed two words describing object features that either evoked (object recall) or did not evoke a semantic concept. Schizophrenia patients tended to overrecall objects for feature pairs that did not describe the same object. Functionally, rostral anterior cingulate cortex (ACC) activation in patients positively correlated with FTD severity during both correct recalled and overrecalled trials. Compared with control subjects, during object recalling, patients overactivated bilateral ACC, temporooccipital junctions, temporal poles and parahippocampi, right inferior frontal gyrus, and dorsolateral prefrontal cortex, but underactivated inferior parietal lobules. Our results support impaired semantic memory retrieval as underlying FTD pathophysiology. Schizophrenia patients showed abnormal activations of brain areas involved in semantic memory, verbal working memory, and initiation and suppression of conflicting responses, which were associated with semantic overrecall and FTD.

  15. Abnormal network connectivity in frontotemporal dementia: evidence for prefrontal isolation.

    PubMed

    Farb, Norman A S; Grady, Cheryl L; Strother, Stephen; Tang-Wai, David F; Masellis, Mario; Black, Sandra; Freedman, Morris; Pollock, Bruce G; Campbell, Karen L; Hasher, Lynn; Chow, Tiffany W

    2013-01-01

    Degraded social function, disinhibition, and stereotypy are defining characteristics of frontotemporal dementia (FTD), manifesting in both the behavioral variant of frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Recent neuroimaging research also associates FTD with alterations in the brain's intrinsic connectivity networks. The present study explored the relationship between neural network connectivity and specific behavioral symptoms in FTD. Resting-state functional magnetic resonance imaging was employed to investigate neural network changes in bvFTD and SD. We used independent components analysis (ICA) to examine changes in frontolimbic network connectivity, as well as several metrics of local network strength, such as the fractional amplitude of low-frequency fluctuations, regional homogeneity, and seed-based functional connectivity. For each analysis, we compared each FTD subgroup to healthy controls, characterizing general and subtype-unique network changes. The relationship between abnormal connectivity in FTD and behavior disturbances was explored. Across multiple analytic approaches, both bvFTD and SD were associated with disrupted frontolimbic connectivity and elevated local connectivity within the prefrontal cortex. Even after controlling for structural atrophy, prefrontal hyperconnectivity was robustly associated with apathy scores. Frontolimbic disconnection was associated with lower disinhibition scores, suggesting that abnormal frontolimbic connectivity contributes to positive symptoms in dementia. Unique to bvFTD, stereotypy was associated with elevated default network connectivity in the right angular gyrus. The behavioral variant was also associated with marginally higher apathy scores and a more diffuse pattern of prefrontal hyperconnectivity than SD. The present findings support a theory of FTD as a disorder of frontolimbic disconnection leading to unconstrained prefrontal connectivity. Prefrontal hyperconnectivity may

  16. Neural decoding with kernel-based metric learning.

    PubMed

    Brockmeier, Austin J; Choi, John S; Kriminger, Evan G; Francis, Joseph T; Principe, Jose C

    2014-06-01

    In studies of the nervous system, the choice of metric for the neural responses is a pivotal assumption. For instance, a well-suited distance metric enables us to gauge the similarity of neural responses to various stimuli and assess the variability of responses to a repeated stimulus-exploratory steps in understanding how the stimuli are encoded neurally. Here we introduce an approach where the metric is tuned for a particular neural decoding task. Neural spike train metrics have been used to quantify the information content carried by the timing of action potentials. While a number of metrics for individual neurons exist, a method to optimally combine single-neuron metrics into multineuron, or population-based, metrics is lacking. We pose the problem of optimizing multineuron metrics and other metrics using centered alignment, a kernel-based dependence measure. The approach is demonstrated on invasively recorded neural data consisting of both spike trains and local field potentials. The experimental paradigm consists of decoding the location of tactile stimulation on the forepaws of anesthetized rats. We show that the optimized metrics highlight the distinguishing dimensions of the neural response, significantly increase the decoding accuracy, and improve nonlinear dimensionality reduction methods for exploratory neural analysis.

  17. Socioeconomic disadvantage and neural development from infancy through early childhood

    PubMed Central

    Chin-Lun Hung, Galen; Hahn, Jill; Alamiri, Bibi; Buka, Stephen L; Goldstein, Jill M; Laird, Nan; Nelson, Charles A; Smoller, Jordan W; Gilman, Stephen E

    2015-01-01

    Background: Early social experiences are believed to shape neurodevelopment, with potentially lifelong consequences. Yet minimal evidence exists regarding the role of the social environment on children’s neural functioning, a core domain of neurodevelopment. Methods: We analysed data from 36 443 participants in the United States Collaborative Perinatal Project, a socioeconomically diverse pregnancy cohort conducted between 1959 and 1974. Study outcomes included: physician (neurologist or paediatrician)-rated neurological abnormality neonatally and thereafter at 4 months and 1 and 7 years; indicators of neurological hard signs and soft signs; and indicators of autonomic nervous system function. Results: Children born to socioeconomically disadvantaged parents were more likely to exhibit neurological abnormalities at 4 months [odds ratio (OR) = 1.20; 95% confidence interval (CI) = 1.06, 1.37], 1 year (OR = 1.35; CI = 1.17, 1.56), and 7 years (OR = 1.67; CI = 1.48, 1.89), and more likely to exhibit neurological hard signs (OR = 1.39; CI = 1.10, 1.76), soft signs (OR = 1.26; CI = 1.09, 1.45) and autonomic nervous system dysfunctions at 7 years. Pregnancy and delivery complications, themselves associated with socioeconomic disadvantage, did not account for the higher risks of neurological abnormalities among disadvantaged children. Conclusions: Parental socioeconomic disadvantage was, independently from pregnancy and delivery complications, associated with abnormal child neural development during the first 7 years of life. These findings reinforce the importance of the early environment for neurodevelopment generally, and expand knowledge regarding the domains of neurodevelopment affected by environmental conditions. Further work is needed to determine the mechanisms linking socioeconomic disadvantage with children’s neural functioning, the timing of such mechanisms and their potential reversibility. PMID:26675752

  18. Buffering social influence: neural correlates of response inhibition predict driving safety in the presence of a peer.

    PubMed

    Cascio, Christopher N; Carp, Joshua; O'Donnell, Matthew Brook; Tinney, Francis J; Bingham, C Raymond; Shope, Jean T; Ouimet, Marie Claude; Pradhan, Anuj K; Simons-Morton, Bruce G; Falk, Emily B

    2015-01-01

    Adolescence is a period characterized by increased sensitivity to social cues, as well as increased risk-taking in the presence of peers. For example, automobile crashes are the leading cause of death for adolescents, and driving with peers increases the risk of a fatal crash. Growing evidence points to an interaction between neural systems implicated in cognitive control and social and emotional context in predicting adolescent risk. We tested such a relationship in recently licensed teen drivers. Participants completed an fMRI session in which neural activity was measured during a response inhibition task, followed by a separate driving simulator session 1 week later. Participants drove alone and with a peer who was randomly assigned to express risk-promoting or risk-averse social norms. The experimentally manipulated social context during the simulated drive moderated the relationship between individual differences in neural activity in the hypothesized cognitive control network (right inferior frontal gyrus, BG) and risk-taking in the driving context a week later. Increased activity in the response inhibition network was not associated with risk-taking in the presence of a risky peer but was significantly predictive of safer driving in the presence of a cautious peer, above and beyond self-reported susceptibility to peer pressure. Individual differences in recruitment of the response inhibition network may allow those with stronger inhibitory control to override risky tendencies when in the presence of cautious peers. This relationship between social context and individual differences in brain function expands our understanding of neural systems involved in top-down cognitive control during adolescent development.

  19. Buffering Social Influence: Neural Correlates of Response Inhibition Predict Driving Safety in the Presence of a Peer

    PubMed Central

    Cascio, Christopher N.; Carp, Joshua; O'Donnell, Matthew Brook; Tinney, Francis J.; Bingham, C. Raymond; Shope, Jean T.; Ouimet, Marie Claude; Pradhan, Anuj K.; Simons-Morton, Bruce G.; Falk, Emily B.

    2016-01-01

    Adolescence is a period characterized by increased sensitivity to social cues, as well as increased risk-taking in the presence of peers. For example, automobile crashes are the leading cause of death for adolescents, and driving with peers increases the risk of a fatal crash. Growing evidence points to an interaction between neural systems implicated in cognitive control and social and emotional context in predicting adolescent risk. We tested such a relationship in recently licensed teen drivers. Participants completed an fMRI session in which neural activity was measured during a response inhibition task, followed by a separate driving simulator session 1 week later. Participants drove alone and with a peer who was randomly assigned to express risk-promoting or risk-averse social norms. The experimentally manipulated social context during the simulated drive moderated the relationship between individual differences in neural activity in the hypothesized cognitive control network (right inferior frontal gyrus, BG) and risk-taking in the driving context a week later. Increased activity in the response inhibition network was not associated with risk-taking in the presence of a risky peer but was significantly predictive of safer driving in the presence of a cautious peer, above and beyond self-reported susceptibility to peer pressure. Individual differences in recruitment of the response inhibition network may allow those with stronger inhibitory control to override risky tendencies when in the presence of cautious peers. This relationship between social context and individual differences in brain function expands our understanding of neural systems involved in top–down cognitive control during adolescent development. PMID:25100217

  20. Neural correlates of treatment response in depressed bipolar adolescents during emotion processing.

    PubMed

    Diler, Rasim Somer; Ladouceur, Cecile D; Segreti, Annamaria; Almeida, Jorge R C; Birmaher, Boris; Axelson, David A; Phillips, Mary L; Pan, Lisa A

    2013-06-01

    Depressive mood in adolescents with bipolar disorder (BDd) is associated with significant morbidity and mortality, but we have limited information about neural correlates of depression and treatment response in BDd. Ten adolescents with BDd (8 females, mean age = 15.6 ± 0.9) completed two (fearful and happy) face gender labeling fMRI experiments at baseline and after 6-weeks of open treatment. Whole-brain analysis was used at baseline to compare their neural activity with those of 10 age and sex-matched healthy controls (HC). For comparisons of the neural activity at baseline and after treatment of youth with BDd, region of interest analysis for dorsal/ventral prefrontal, anterior cingulate, and amygdala activity, and significant regions identified by wholebrain analysis between BDd and HC were analyzed. There was significant improvement in depression scores (mean percentage change on the Child Depression Rating Scale-Revised 57 % ± 28). Neural activity after treatment was decreased in left occipital cortex in the intense fearful experiment, but increased in left insula, left cerebellum, and right ventrolateral prefrontal cortex in the intense happy experiment. Greater improvement in depression was associated with baseline higher activity in ventral ACC to mild happy faces. Study sample size was relatively small for subgroup analysis and consisted of mainly female adolescents that were predominantly on psychotropic medications during scanning. Our results of reduced negative emotion processing versus increased positive emotion processing after treatment of depression (improvement of cognitive bias to negative and away from positive) are consistent with the improvement of depression according to Beck's cognitive theory.

  1. Reward abnormalities among women with full and subthreshold bulimia nervosa: a functional magnetic resonance imaging study.

    PubMed

    Bohon, Cara; Stice, Eric

    2011-11-01

    To test the hypothesis that women with full and subthreshold bulimia nervosa show abnormal neural activation in response to food intake and anticipated food intake relative to healthy control women. Females with and without full/subthreshold bulimia nervosa recruited from the community (N = 26) underwent functional magnetic resonance imaging (fMRI) during receipt and anticipated receipt of chocolate milkshake and a tasteless control solution. Women with bulimia nervosa showed trends for less activation than healthy controls in the right anterior insula in response to anticipated receipt of chocolate milkshake (vs. tasteless solution) and in the left middle frontal gyrus, right posterior insula, right precentral gyrus, and right mid dorsal insula in response to consumptions of milkshake (vs. tasteless solution). Bulimia nervosa may be related to potential hypofunctioning of the brain reward system, which may lead these individuals to binge eat to compensate for this reward deficit, though the hypo-responsivity might be a result of a history of binge eating highly palatable foods. Copyright © 2010 Wiley Periodicals, Inc.

  2. Reward Abnormalities Among Women with Full and Subthreshold Bulimia Nervosa: A Functional Magnetic Resonance Imaging Study

    PubMed Central

    Bohon, Cara; Stice, Eric

    2010-01-01

    Objective To test the hypothesis that women with full and subthreshold bulimia nervosa show abnormal neural activation in response to food intake and anticipated food intake relative to healthy control women. Method Females with and without full/subthreshold bulimia nervosa recruited from the community (N = 26) underwent functional magnetic resonance imaging (fMRI) during receipt and anticipated receipt of chocolate milkshake and a tasteless control solution. Results Women with bulimia nervosa showed trends for less activation than healthy controls in the right anterior insula in response to anticipated receipt of chocolate milkshake (versus tasteless solution) and in the left middle frontal gyrus, right posterior insula, right precentral gyrus, and right mid dorsal insula in response to consumptions of milkshake (versus tasteless solution). Discussion Bulimia nervosa may be related to potential hypo-functioning of the brain reward system, which may lead these individuals to binge eat to compensate for this reward deficit, though the hypo-responsivity might be a result of a history of binge eating highly palatable foods. PMID:21997421

  3. Developmental abnormalities of the posterior pituitary gland.

    PubMed

    di Iorgi, Natascia; Secco, Andrea; Napoli, Flavia; Calandra, Erika; Rossi, Andrea; Maghnie, Mohamad

    2009-01-01

    While the molecular mechanisms of anterior pituitary development are now better understood than in the past, both in animals and in humans, little is known about the mechanisms regulating posterior pituitary development. The posterior pituitary gland is formed by the evagination of neural tissue from the floor of the third ventricle. It consists of the distal axons of the hypothalamic magnocellular neurones that shape the neurohypophysis. After its downward migration, it is encapsulated together with the ascending ectodermal cells of Rathke's pouch which form the anterior pituitary. By the end of the first trimester, this development is completed and vasopressin and oxytocin can be detected in neurohypophyseal tissue. Abnormal posterior pituitary migration such as the ectopic posterior pituitary lobe appearing at the level of median eminence or along the pituitary stalk have been reported in idiopathic GH deficiency or in subjects with HESX1, LHX4 and SOX3 gene mutations. Another intriguing feature of abnormal posterior pituitary development involves genetic forms of posterior pituitary neurodegeneration that have been reported in autosomal-dominant central diabetes insipidus and Wolfram disease. Defining the phenotype of the posterior pituitary gland can have significant clinical implications for management and counseling, as well as providing considerable insight into normal and abnormal mechanisms of posterior pituitary development in humans.

  4. External motivation to avoid prejudice alters neural responses to targets varying in race and status

    PubMed Central

    Mattan, Bradley D; Kubota, Jennifer T; Dang, Tzipporah P

    2018-01-01

    Abstract Those who are high in external motivation to respond without prejudice (EMS) tend to focus on non-racial attributes when describing others. This fMRI study examined the neural processing of race and an alternative yet stereotypically relevant attribute (viz., socioeconomic status: SES) as a function of the perceiver’s EMS. Sixty-one White participants privately formed impressions of Black and White faces ascribed with high or low SES. Analyses focused on regions supporting race- and status-based reward/salience (NAcc), evaluation (VMPFC) and threat/relevance (amygdala). Consistent with previous findings from the literature on status-based evaluation, we observed greater neural responses to high-status (vs low-status) targets in all regions of interest when participants were relatively low in EMS. In contrast, we observed the opposite pattern when participants were relatively high in EMS. Notably, all effects were independent of target race. In summary, White perceivers’ race-related motivations similarly altered their neural responses to the SES of Black and White targets. Specifically, the findings suggest that EMS may attenuate the positive value and/or salience of high status in a mixed-race context. Findings are discussed in the context of the stereotypic relationship between race and SES. PMID:29077925

  5. Neural response to pictorial health warning labels can predict smoking behavioral change

    PubMed Central

    Riddle, Philip J.; Newman-Norlund, Roger D.; Baer, Jessica; Thrasher, James F.

    2016-01-01

    In order to improve our understanding of how pictorial health warning labels (HWLs) influence smoking behavior, we examined whether brain activity helps to explain smoking behavior above and beyond self-reported effectiveness of HWLs. We measured the neural response in the ventromedial prefrontal cortex (vmPFC) and the amygdala while adult smokers viewed HWLs. Two weeks later, participants’ self-reported smoking behavior and biomarkers of smoking behavior were reassessed. We compared multiple models predicting change in self-reported smoking behavior (cigarettes per day [CPD]) and change in a biomarkers of smoke exposure (expired carbon monoxide [CO]). Brain activity in the vmPFC and amygdala not only predicted changes in CO, but also accounted for outcome variance above and beyond self-report data. Neural data were most useful in predicting behavioral change as quantified by the objective biomarker (CO). This pattern of activity was significantly modulated by individuals’ intention to quit. The finding that both cognitive (vmPFC) and affective (amygdala) brain areas contributed to these models supports the idea that smokers respond to HWLs in a cognitive-affective manner. Based on our findings, researchers may wish to consider using neural data from both cognitive and affective networks when attempting to predict behavioral change in certain populations (e.g. cigarette smokers). PMID:27405615

  6. Effects of expectancy and abstinence on the neural response to smoking cues in cigarette smokers: an fMRI study.

    PubMed

    McBride, Dharma; Barrett, Sean P; Kelly, Jared T; Aw, Andrew; Dagher, Alain

    2006-12-01

    Cues associated with drug taking can trigger relapse, drug seeking, and craving in addicted individuals. Behavioral studies suggest that drug availability and withdrawal can affect the individual response to drug cues. Moreover, the importance of subjective craving in cue-induced relapse has been questioned and an alternative model put forward according to which drug cues trigger habitual drug-seeking behaviors independently of craving. We used functional magnetic resonance imaging to compare the brain response to smoking and control videotapes in 20 healthy smokers, while varying their expectancy to smoke and abstinence levels. The neural response to cigarette cues was strongly modulated by expectancy and, to a lesser extent, abstinence. In people expecting to smoke immediately after the scan, smoking cues activated brain areas implicated in arousal, attention, and cognitive control. However, when subjects knew they would not be allowed to smoke for 4 h, there was almost no brain activation in response to smoking cues, despite equivalent reported levels of craving. In the dorsolateral prefrontal cortex, the neural response was a function of both craving and expectancy. Thalamo-cingulate connectivity, thought to be an index of arousal, was greater during expectancy than nonexpectancy. Our findings confirm the importance of expectancy in the neural response to drug cues, and lend support to the theory that these cues act on brain areas involved in arousal and attention.

  7. Training and Validating a Deep Convolutional Neural Network for Computer-Aided Detection and Classification of Abnormalities on Frontal Chest Radiographs.

    PubMed

    Cicero, Mark; Bilbily, Alexander; Colak, Errol; Dowdell, Tim; Gray, Bruce; Perampaladas, Kuhan; Barfett, Joseph

    2017-05-01

    Convolutional neural networks (CNNs) are a subtype of artificial neural network that have shown strong performance in computer vision tasks including image classification. To date, there has been limited application of CNNs to chest radiographs, the most frequently performed medical imaging study. We hypothesize CNNs can learn to classify frontal chest radiographs according to common findings from a sufficiently large data set. Our institution's research ethics board approved a single-center retrospective review of 35,038 adult posterior-anterior chest radiographs and final reports performed between 2005 and 2015 (56% men, average age of 56, patient type: 24% inpatient, 39% outpatient, 37% emergency department) with a waiver for informed consent. The GoogLeNet CNN was trained using 3 graphics processing units to automatically classify radiographs as normal (n = 11,702) or into 1 or more of cardiomegaly (n = 9240), consolidation (n = 6788), pleural effusion (n = 7786), pulmonary edema (n = 1286), or pneumothorax (n = 1299). The network's performance was evaluated using receiver operating curve analysis on a test set of 2443 radiographs with the criterion standard being board-certified radiologist interpretation. Using 256 × 256-pixel images as input, the network achieved an overall sensitivity and specificity of 91% with an area under the curve of 0.964 for classifying a study as normal (n = 1203). For the abnormal categories, the sensitivity, specificity, and area under the curve, respectively, were 91%, 91%, and 0.962 for pleural effusion (n = 782), 82%, 82%, and 0.868 for pulmonary edema (n = 356), 74%, 75%, and 0.850 for consolidation (n = 214), 81%, 80%, and 0.875 for cardiomegaly (n = 482), and 78%, 78%, and 0.861 for pneumothorax (n = 167). Current deep CNN architectures can be trained with modest-sized medical data sets to achieve clinically useful performance at detecting and excluding common pathology on chest radiographs.

  8. Integrating the behavioral and neural dynamics of response selection in a dual-task paradigm: a dynamic neural field model of Dux et al. (2009).

    PubMed

    Buss, Aaron T; Wifall, Tim; Hazeltine, Eliot; Spencer, John P

    2014-02-01

    People are typically slower when executing two tasks than when only performing a single task. These dual-task costs are initially robust but are reduced with practice. Dux et al. (2009) explored the neural basis of dual-task costs and learning using fMRI. Inferior frontal junction (IFJ) showed a larger hemodynamic response on dual-task trials compared with single-task trial early in learning. As dual-task costs were eliminated, dual-task hemodynamics in IFJ reduced to single-task levels. Dux and colleagues concluded that the reduction of dual-task costs is accomplished through increased efficiency of information processing in IFJ. We present a dynamic field theory of response selection that addresses two questions regarding these results. First, what mechanism leads to the reduction of dual-task costs and associated changes in hemodynamics? We show that a simple Hebbian learning mechanism is able to capture the quantitative details of learning at both the behavioral and neural levels. Second, is efficiency isolated to cognitive control areas such as IFJ, or is it also evident in sensory motor areas? To investigate this, we restrict Hebbian learning to different parts of the neural model. None of the restricted learning models showed the same reductions in dual-task costs as the unrestricted learning model, suggesting that efficiency is distributed across cognitive control and sensory motor processing systems.

  9. Beauty is in the belief of the beholder: cognitive influences on the neural response to facial attractiveness.

    PubMed

    Thiruchselvam, Ravi; Harper, Jessica; Homer, Abigail L

    2016-12-01

    Judgments of facial attractiveness are central to decision-making in various domains, but little is known about the extent to which they are malleable. In this study, we used EEG/ERP methods to examine two novel influences on neural and subjective responses to facial attractiveness: an observer's expectation and repetition. In each trial of our task, participants viewed either an ordinary or attractive face. To alter expectations, the faces were preceded by a peer-rating that ostensibly reflected the overall attractiveness value assigned to that face by other individuals. To examine the impact of repetition, trials were presented twice throughout the experimental session. Results showed that participants' expectations about a person's attractiveness level powerfully altered both the neural response (i.e. the late positive potential; LPP) and self-reported attractiveness ratings. Intriguingly, repetition enhanced both the LPP and self-reported attractiveness as well. Exploratory analyses further suggested that both observer expectation and repetition modulated early neural responses (i.e. the early posterior negativity; EPN) elicited by facial attractiveness. Collectively, these results highlight novel influences on a core social judgment that underlies individuals' affective lives. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  10. Candy and the brain: neural response to candy gains and losses.

    PubMed

    Luking, Katherine R; Barch, Deanna M

    2013-09-01

    Incentive processing is a critical component of a host of cognitive processes, including attention, motivation, and learning. Neuroimaging studies have clarified the neural systems underlying processing of primary and secondary rewards in adults. However, current reward paradigms have hindered comparisons across these reward types as well as between age groups. To address methodological issues regarding the timing of incentive delivery (during scan vs. postscan) and the age-appropriateness of the incentive type, we utilized fMRI and a modified version of a card-guessing game (CGG), in which candy pieces delivered postscan served as the reinforcer, to investigate neural responses to incentives. Healthy young adults 22-26 years of age won and lost large and small amounts of candy on the basis of their ability to guess the number on a mystery card. BOLD activity was compared following candy gain (large/small), loss (large/small), and neutral feedback. During candy gains, adults recruited regions typically involved in response to monetary and other rewards, such as the caudate, putamen, and orbitofrontal cortex. During losses, they displayed greater deactivation in the hippocampus than in response to neutral and gain feedback. Additionally, individual-difference analyses suggested a negative relationship between reward sensitivity (assessed by the Behavioral Inhibition/Behavioral Activation Scales) and the difference between high- and low-magnitude losses in the caudate and lateral orbitofrontal cortex. Also within the striatum, greater punishment sensitivity was positively related to the difference in activity following high as compared to low gains. Overall, these results show strong overlap with those from previous monetary versions of the CGG and provide a baseline for future work with developmental populations.

  11. Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer.

    PubMed

    Xia, Shu; Kohli, Manish; Du, Meijun; Dittmar, Rachel L; Lee, Adam; Nandy, Debashis; Yuan, Tiezheng; Guo, Yongchen; Wang, Yuan; Tschannen, Michael R; Worthey, Elizabeth; Jacob, Howard; See, William; Kilari, Deepak; Wang, Xuexia; Hovey, Raymond L; Huang, Chiang-Ching; Wang, Liang

    2015-06-30

    Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival (p < 0.04). After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair, and chemotherapy resistance. These changes may reflect the dynamic evolution of heterozygous tumor populations in response to these treatments. These results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer.

  12. Proportionate Responses to Life Events Influence Clinicians' Judgments of Psychological Abnormality

    ERIC Educational Resources Information Center

    Kim, Nancy S.; Paulus, Daniel J.; Gonzalez, Jeffrey S.; Khalife, Danielle

    2012-01-01

    Psychological abnormality is a fundamental concept in the "Diagnostic and Statistical Manual of Mental Disorders" ("DSM-IV-TR"; American Psychiatric Association, 2000) and in all clinical evaluations. How do practicing clinical psychologists use the context of life events to judge the abnormality of a person's current behaviors? The appropriate…

  13. Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development.

    PubMed

    Storer, Mekayla A; Gallagher, Denis; Fatt, Michael P; Simonetta, Jaclin V; Kaplan, David R; Miller, Freda D

    2018-05-08

    Circulating systemic factors can regulate adult neural stem cell (NSC) biology, but the identity of these circulating cues is still being defined. Here, we have focused on the cytokine interleukin-6 (IL-6), since increased circulating levels of IL-6 are associated with neural pathologies such as autism and bipolar disorder. We show that IL-6 promotes proliferation of post-natal murine forebrain NSCs and that, when the IL-6 receptor is inducibly knocked out in post-natal or adult neural precursors, this causes a long-term decrease in forebrain NSCs. Moreover, a transient circulating surge of IL-6 in perinatal or adult mice causes an acute increase in neural precursor proliferation followed by long-term depletion of adult NSC pools. Thus, IL-6 signaling is both necessary and sufficient for adult NSC self-renewal, and acute perturbations in circulating IL-6, as observed in many pathological situations, have long-lasting effects on the size of adult NSC pools. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Prediction of air pollutant concentration based on sparse response back-propagation training feedforward neural networks.

    PubMed

    Ding, Weifu; Zhang, Jiangshe; Leung, Yee

    2016-10-01

    In this paper, we predict air pollutant concentration using a feedforward artificial neural network inspired by the mechanism of the human brain as a useful alternative to traditional statistical modeling techniques. The neural network is trained based on sparse response back-propagation in which only a small number of neurons respond to the specified stimulus simultaneously and provide a high convergence rate for the trained network, in addition to low energy consumption and greater generalization. Our method is evaluated on Hong Kong air monitoring station data and corresponding meteorological variables for which five air quality parameters were gathered at four monitoring stations in Hong Kong over 4 years (2012-2015). Our results show that our training method has more advantages in terms of the precision of the prediction, effectiveness, and generalization of traditional linear regression algorithms when compared with a feedforward artificial neural network trained using traditional back-propagation.

  15. The effectiveness of airline pilot training for abnormal events.

    PubMed

    Casner, Stephen M; Geven, Richard W; Williams, Kent T

    2013-06-01

    To evaluate the effectiveness of airline pilot training for abnormal in-flight events. Numerous accident reports describe situations in which pilots responded to abnormal events in ways that were different from what they had practiced many times before. One explanation for these missteps is that training and testing for these skills have become a highly predictable routine for pilots who arrive to the training environment well aware of what to expect. Under these circumstances, pilots get plentiful practice in responding to abnormal events but may get little practice in recognizing them and deciding which responses to offer. We presented 18 airline pilots with three abnormal events that are required during periodic training and testing. Pilots were presented with each event under the familiar circumstances used during training and also under less predictable circumstances as they might occur during flight. When presented in the routine ways seen during training, pilots gave appropriate responses and showed little variability. However, when the abnormal events were presented unexpectedly, pilots' responses were less appropriate and showed great variability from pilot to pilot. The results suggest that the training and testing practices used in airline training may result in rote-memorized skills that are specific to the training situation and that offer modest generalizability to other situations. We recommend a more complete treatment of abnormal events that allows pilots to practice recognizing the event and choosing and recalling the appropriate response. The results will aid the improvement of existing airline training practices.

  16. Automated radial basis function neural network based image classification system for diabetic retinopathy detection in retinal images

    NASA Astrophysics Data System (ADS)

    Anitha, J.; Vijila, C. Kezi Selva; Hemanth, D. Jude

    2010-02-01

    Diabetic retinopathy (DR) is a chronic eye disease for which early detection is highly essential to avoid any fatal results. Image processing of retinal images emerge as a feasible tool for this early diagnosis. Digital image processing techniques involve image classification which is a significant technique to detect the abnormality in the eye. Various automated classification systems have been developed in the recent years but most of them lack high classification accuracy. Artificial neural networks are the widely preferred artificial intelligence technique since it yields superior results in terms of classification accuracy. In this work, Radial Basis function (RBF) neural network based bi-level classification system is proposed to differentiate abnormal DR Images and normal retinal images. The results are analyzed in terms of classification accuracy, sensitivity and specificity. A comparative analysis is performed with the results of the probabilistic classifier namely Bayesian classifier to show the superior nature of neural classifier. Experimental results show promising results for the neural classifier in terms of the performance measures.

  17. Small Airway Dysfunction and Abnormal Exercise Responses

    PubMed Central

    Petsonk, Edward L.; Stansbury, Robert C.; Beeckman-Wagner, Lu-Ann; Long, Joshua L.; Wang, Mei Lin

    2016-01-01

    Rationale Coal mine dust exposure can cause symptoms and loss of lung function from multiple mechanisms, but the roles of each disease process are not fully understood. Objectives We investigated the implications of small airway dysfunction for exercise physiology among a group of workers exposed to coal mine dust. Methods Twenty coal miners performed spirometry, first breathing air and then helium-oxygen, single-breath diffusing capacity, and computerized chest tomography, and then completed cardiopulmonary exercise testing. Measurements and Main Results Six participants meeting criteria for small airway dysfunction were compared with 14 coal miners who did not. At submaximal workload, miners with small airway dysfunction used a higher proportion of their maximum voluntary ventilation and had higher ventilatory equivalents for both O2 and CO2. Regression modeling indicated that inefficient ventilation was significantly related to small airway dysfunction but not to FEV1 or diffusing capacity. At the end of exercise, miners with small airway dysfunction had 27% lower O2 consumption. Conclusions Small airway abnormalities may be associated with important inefficiency of exercise ventilation. In dust-exposed individuals with only mild abnormalities on resting lung function tests or chest radiographs, cardiopulmonary exercise testing may be important in defining causes of exercise intolerance. PMID:27073987

  18. Reduced expression of the NMDA receptor-interacting protein SynGAP causes behavioral abnormalities that model symptoms of Schizophrenia.

    PubMed

    Guo, Xiaochuan; Hamilton, Peter J; Reish, Nicholas J; Sweatt, J David; Miller, Courtney A; Rumbaugh, Gavin

    2009-06-01

    Abnormal function of NMDA receptors is believed to be a contributing factor to the pathophysiology of schizophrenia. NMDAR subunits and postsynaptic-interacting proteins of these channels are abnormally expressed in some patients with this illness. In mice, reduced NMDAR expression leads to behaviors analogous to symptoms of schizophrenia, but reports of animals with mutations in core postsynaptic density proteins having similar a phenotype have yet to be reported. Here we show that reduced expression of the neuronal RasGAP and NMDAR-associated protein, SynGAP, results in abnormal behaviors strikingly similar to that reported in mice with reduced NMDAR function. SynGAP mutant mice exhibited nonhabituating and persistent hyperactivity that was ameliorated by the antipsychotic clozapine. An NMDAR antagonist, MK-801, induced hyperactivity in normal mice but SynGAP mutants were less responsive, suggesting that NMDAR hypofunction contributes to this behavioral abnormality. SynGAP mutants exhibited enhanced startle reactivity and impaired sensory-motor gating. These mice also displayed a complete lack of social memory and a propensity toward social isolation. Finally, SynGAP mutants had deficits in cued fear conditioning and working memory, indicating abnormal function of circuits that control emotion and choice. Our results demonstrate that SynGAP mutant mice have gross neurological deficits similar to other mouse models of schizophrenia. Because SynGAP interacts with NMDARs, and the signaling activity of this protein is regulated by these channels, our data in dicate that SynGAP lies downstream of NMDARs and is a required intermediate for normal neural circuit function and behavior. Taken together, these data support the idea that schizophrenia may arise from abnormal signaling pathways that are mediated by NMDA receptors.

  19. Poly(ADP-ribose) polymerase-1 (Parp-1)-deficient mice demonstrate abnormal antibody responses

    PubMed Central

    Ambrose, Helen E; Willimott, Shaun; Beswick, Richard W; Dantzer, Françoise; de Murcia, Josiane Ménissier; Yelamos, José; Wagner, Simon D

    2009-01-01

    Poly(ADP-ribosylation) of acceptor proteins is an epigenetic modification involved in DNA strand break repair, recombination and transcription. Here we provide evidence for the involvement of poly(ADP-ribose) polymerase-1 (Parp-1) in antibody responses. Parp-1−/− mice had increased numbers of T cells and normal numbers of total B cells. Marginal zone B cells were mildly reduced in number, and numbers of follicular B cells were preserved. There were abnormal levels of basal immunoglobulins, with reduced levels of immunoglobulin G2a (IgG2a) and increased levels of IgA and IgG2b. Analysis of specific antibody responses showed that T cell-independent responses were normal but T cell-dependent responses were markedly reduced. Germinal centres were normal in size and number. In vitro purified B cells from Parp-1−/− mice proliferated normally and showed normal IgM secretion, decreased switching to IgG2a but increased IgA secretion. Collectively our results demonstrate that Parp-1 has essential roles in normal T cell-dependent antibody responses and the regulation of isotype expression. We speculate that Parp-1 forms a component of the protein complex involved in resolving the DNA double-strand breaks that occur during class switch recombination. PMID:18778284

  20. Reduced neural activity of the prefrontal cognitive control circuitry during response inhibition to negative words in people with schizophrenia

    PubMed Central

    Vercammen, Ans; Morris, Richard; Green, Melissa J.; Lenroot, Rhoshel; Kulkarni, Jayashri; Carr, Vaughan J.; Weickert, Cynthia Shannon; Weickert, Thomas W.

    2012-01-01

    Background Schizophrenia is characterized by deficits in executive control and impairments in emotion processing. This study assessed the nature and extent of potential alterations in the neural substrates supporting the interaction between cognitive control mechanisms and emotion attribution processes in people with schizophrenia. Methods Functional magnetic resonance imaging was performed during a verbal emotional go/no-go task. People with schizophrenia and healthy controls responded to word stimuli of a prespecified emotional valence (positive, negative or neutral) while inhibiting responses to stimuli of a different valence. Results We enrolled 20 people with schizophrenia and 23 controls in the study. Healthy controls activated an extensive dorsal prefrontal–parietal network while inhibiting responses to negative words compared to neutral words, but showed deactivation of the midcingulate cortex while inhibiting responses to positive words compared to neutral words. People with schizophrenia failed to activate this network during response inhibition to negative words, whereas during response inhibition to positive words they did not deactivate the cingulate, but showed increased responsivity in the frontal cortex. Limitations Sample heterogeneity is characteristic of studies of schizophrenia and may have contributed to more variable neural responses in the patient sample despite the care taken to control for potentially confounding variables. Conclusion Our results showed that schizophrenia is associated with aberrant modulation of neural responses during the interaction between cognitive control and emotion processing. Failure of the frontal circuitry to regulate goal-directed behaviour based on emotion attributions may contribute to deficits in psychosocial functioning in daily life. PMID:22617625

  1. Neural response to reward anticipation under risk is nonlinear in probabilities.

    PubMed

    Hsu, Ming; Krajbich, Ian; Zhao, Chen; Camerer, Colin F

    2009-02-18

    A widely observed phenomenon in decision making under risk is the apparent overweighting of unlikely events and the underweighting of nearly certain events. This violates standard assumptions in expected utility theory, which requires that expected utility be linear (objective) in probabilities. Models such as prospect theory have relaxed this assumption and introduced the notion of a "probability weighting function," which captures the key properties found in experimental data. This study reports functional magnetic resonance imaging (fMRI) data that neural response to expected reward is nonlinear in probabilities. Specifically, we found that activity in the striatum during valuation of monetary gambles are nonlinear in probabilities in the pattern predicted by prospect theory, suggesting that probability distortion is reflected at the level of the reward encoding process. The degree of nonlinearity reflected in individual subjects' decisions is also correlated with striatal activity across subjects. Our results shed light on the neural mechanisms of reward processing, and have implications for future neuroscientific studies of decision making involving extreme tails of the distribution, where probability weighting provides an explanation for commonly observed behavioral anomalies.

  2. The modified gait abnormality rating scale in patients with a conversion disorder: a reliability and responsiveness study.

    PubMed

    Vandenberg, Justin M; George, Deanna R; O'Leary, Andrea J; Olson, Lindsay C; Strassburg, Kaitlyn R; Hollman, John H

    2015-01-01

    Individuals with conversion disorder have neurologic symptoms that are not identified by an underlying organic cause. Often the symptoms manifest as gait disturbances. The modified gait abnormality rating scale (GARS-M) may be useful for quantifying gait abnormalities in these individuals. The purpose of this study was to examine the reliability, responsiveness and concurrent validity of GARS-M scores in individuals with conversion disorder. Data from 27 individuals who completed a rehabilitation program were included in this study. Pre- and post-intervention videos were obtained and walking speed was measured. Five examiners independently evaluated gait performance according to the GARS-M criteria. Inter- and intrarater reliability of GARS-M scores were estimated with intraclass correlation coefficients (ICCs). Responsiveness was estimated with the minimum detectable change (MDC). Pre- to post-treatment changes in GARS-M scores were analyzed with a dependent t-test. The correlation between GARS-M scores and walking speed was analyzed to assess concurrent validity. GARS-M scores were quantified with good-to-excellent inter- (ICC = 0.878) and intrarater reliability (ICC = 0.989). The MDC was 2 points. Mean GARS-M scores decreased from 7 ± 5 at baseline to 1 ± 2 at discharge (t26 = 7.411, p < 0.001) and 85% of patients improved beyond the MDC. Furthermore, GARS-M scores and walking speed measurements were moderately correlated (r = -0.582, p = 0.004), indicating that the GARS-M has acceptable concurrent validity. Our findings provide evidence that the GARS-M scores are reliable, valid and responsive for quantifying gait abnormalities in patients with conversion disorder. GARS-M scores provide objective measures upon which treatment effects can be assessed. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. The Involvement of Endogenous Neural Oscillations in the Processing of Rhythmic Input: More Than a Regular Repetition of Evoked Neural Responses

    PubMed Central

    Zoefel, Benedikt; ten Oever, Sanne; Sack, Alexander T.

    2018-01-01

    It is undisputed that presenting a rhythmic stimulus leads to a measurable brain response that follows the rhythmic structure of this stimulus. What is still debated, however, is the question whether this brain response exclusively reflects a regular repetition of evoked responses, or whether it also includes entrained oscillatory activity. Here we systematically present evidence in favor of an involvement of entrained neural oscillations in the processing of rhythmic input while critically pointing out which questions still need to be addressed before this evidence could be considered conclusive. In this context, we also explicitly discuss the potential functional role of such entrained oscillations, suggesting that these stimulus-aligned oscillations reflect, and serve as, predictive processes, an idea often only implicitly assumed in the literature. PMID:29563860

  4. Male Killing Spiroplasma Preferentially Disrupts Neural Development in the Drosophila melanogaster Embryo

    PubMed Central

    Martin, Jennifer; Chong, Trisha; Ferree, Patrick M.

    2013-01-01

    Male killing bacteria such as Spiroplasma are widespread pathogens of numerous arthropods including Drosophila melanogaster. These maternally transmitted bacteria can bias host sex ratios toward the female sex in order to ‘selfishly’ enhance bacterial transmission. However, little is known about the specific means by which these pathogens disrupt host development in order to kill males. Here we show that a male-killing Spiroplasma strain severely disrupts nervous tissue development in male but not female D. melanogaster embryos. The neuroblasts, or neuron progenitors, form properly and their daughter cells differentiate into neurons of the ventral nerve chord. However, the neurons fail to pack together properly and they produce highly abnormal axons. In contrast, non-neural tissue, such as mesoderm, and body segmentation appear normal during this time, although the entire male embryo becomes highly abnormal during later stages. Finally, we found that Spiroplasma is altogether absent from the neural tissue but localizes within the gut and the epithelium immediately surrounding the neural tissue, suggesting that the bacterium secretes a toxin that affects neural tissue development across tissue boundaries. Together these findings demonstrate the unique ability of this insect pathogen to preferentially affect development of a specific embryonic tissue to induce male killing. PMID:24236124

  5. Response to an Abnormal Ovarian Cancer Screening Test Result: Test of the Social Cognitive Processing and Cognitive Social Health Information Processing Models

    PubMed Central

    Andrykowski, Michael A.; Pavlik, Edward J.

    2009-01-01

    All cancer screening tests produce a proportion of abnormal results requiring follow-up. Consequently, the cancer screening setting is a natural laboratory for examining psychological and behavioral response to a threatening health-related event. This study tested hypotheses derived from the Social Cognitive Processing and Cognitive-Social Health Information Processing models in trying to understand response to an abnormal ovarian cancer (OC) screening test result. Women (n=278) receiving an abnormal screening test result a mean of 7 weeks earlier were assessed prior to a repeat screening test intended to clarify their previous abnormal result. Measures of disposition (optimism, informational coping style), social environment (social support and constraint), emotional processing, distress, and benefit finding were obtained. Regression analyses indicated greater distress was associated with greater social constraint and emotional processing and a monitoring coping style in women with a family history of OC. Distress was unrelated to social support. Greater benefit finding was associated with both greater social constraint and support and greater distress. The primacy of social constraint in accounting for both benefit-finding and distress was noteworthy and warrants further research on the role of social constraint in adaptation to stressful events. PMID:20419561

  6. Transient Modulations of Neural Responses to Heartbeats Covary with Bodily Self-Consciousness.

    PubMed

    Park, Hyeong-Dong; Bernasconi, Fosco; Bello-Ruiz, Javier; Pfeiffer, Christian; Salomon, Roy; Blanke, Olaf

    2016-08-10

    Recent research has investigated self-consciousness associated with the multisensory processing of bodily signals (e.g., somatosensory, visual, vestibular signals), a notion referred to as bodily self-consciousness, and these studies have shown that the manipulation of bodily inputs induces changes in bodily self-consciousness such as self-identification. Another line of research has highlighted the importance of signals from the inside of the body (e.g., visceral signals) and proposed that neural representations of internal bodily signals underlie self-consciousness, which to date has been based on philosophical inquiry, clinical case studies, and behavioral studies. Here, we investigated the relationship of bodily self-consciousness with the neural processing of internal bodily signals. By combining electrical neuroimaging, analysis of peripheral physiological signals, and virtual reality technology in humans, we show that transient modulations of neural responses to heartbeats in the posterior cingulate cortex covary with changes in bodily self-consciousness induced by the full-body illusion. Additional analyses excluded that measured basic cardiorespiratory parameters or interoceptive sensitivity traits could account for this finding. These neurophysiological data link experimentally the cortical mapping of the internal body to self-consciousness. What are the brain mechanisms of self-consciousness? Prominent views propose that the neural processing associated with signals from the internal organs (such as the heart and the lung) plays a critical role in self-consciousness. Although this hypothesis dates back to influential views in philosophy and psychology (e.g., William James), definitive experimental evidence supporting this idea is lacking despite its recent impact in neuroscience. In the present study, we show that posterior cingulate activities responding to heartbeat signals covary with changes in participants' conscious self-identification with a body

  7. Attention Strongly Modulates Reliability of Neural Responses to Naturalistic Narrative Stimuli.

    PubMed

    Ki, Jason J; Kelly, Simon P; Parra, Lucas C

    2016-03-09

    Attentional engagement is a major determinant of how effectively we gather information through our senses. Alongside the sheer growth in the amount and variety of information content that we are presented with through modern media, there is increased variability in the degree to which we "absorb" that information. Traditional research on attention has illuminated the basic principles of sensory selection to isolated features or locations, but it provides little insight into the neural underpinnings of our attentional engagement with modern naturalistic content. Here, we show in human subjects that the reliability of an individual's neural responses with respect to a larger group provides a highly robust index of the level of attentional engagement with a naturalistic narrative stimulus. Specifically, fast electroencephalographic evoked responses were more strongly correlated across subjects when naturally attending to auditory or audiovisual narratives than when attention was directed inward to a mental arithmetic task during stimulus presentation. This effect was strongest for audiovisual stimuli with a cohesive narrative and greatly reduced for speech stimuli lacking meaning. For compelling audiovisual narratives, the effect is remarkably strong, allowing perfect discrimination between attentional state across individuals. Control experiments rule out possible confounds related to altered eye movement trajectories or order of presentation. We conclude that reliability of evoked activity reproduced across subjects viewing the same movie is highly sensitive to the attentional state of the viewer and listener, which is aided by a cohesive narrative. Copyright © 2016 Ki et al.

  8. Improving Neural Recording Technology at the Nanoscale

    NASA Astrophysics Data System (ADS)

    Ferguson, John Eric

    Neural recording electrodes are widely used to study normal brain function (e.g., learning, memory, and sensation) and abnormal brain function (e.g., epilepsy, addiction, and depression) and to interface with the nervous system for neuroprosthetics. With a deep understanding of the electrode interface at the nanoscale and the use of novel nanofabrication processes, neural recording electrodes can be designed that surpass previous limits and enable new applications. In this thesis, I will discuss three projects. In the first project, we created an ultralow-impedance electrode coating by controlling the nanoscale texture of electrode surfaces. In the second project, we developed a novel nanowire electrode for long-term intracellular recordings. In the third project, we created a means of wirelessly communicating with ultra-miniature, implantable neural recording devices. The techniques developed for these projects offer significant improvements in the quality of neural recordings. They can also open the door to new types of experiments and medical devices, which can lead to a better understanding of the brain and can enable novel and improved tools for clinical applications.

  9. Experimental Evaluation of Grid Support Enabled PV Inverter Response to Abnormal Grid Conditions: Preprint

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nelson, Austin; Martin, Gregory; Hurtt, James

    As revised interconnection standards for grid-tied photovoltaic (PV) inverters address new advanced grid support functions (GSFs), there is increasing interest in inverter performance in the case of abnormal grid conditions. The growth of GSF-enabled inverters has outpaced the industry standards that define their operation, although recently published updates to UL1741 with Supplement SA define test conditions for GSFs such as volt-var control, frequency-watt control, and volt-age/frequency ride-through, among others. A comparative experimental evaluation has been completed on four commercially available, three-phase PV inverters in the 24.0-39.8 kVA power range on their GSF capability and the effect on abnormal grid conditionmore » response. This study examines the impact particular GSF implementations have on run-on times during islanding conditions, peak voltages in load rejection overvoltage scenarios, and peak currents during single-phase and three-phase fault events for individual inverters. This report reviews comparative test data, which shows that GSFs have little impact on the metrics of interest in most tests cases.« less

  10. Wall Thickness, Pulmonary Hypertension, and Diastolic Filling Abnormalities Predict Response to Postoperative Biventricular Pacing

    PubMed Central

    Brusen, Robin M.; Hahn, Rebecca; Cabreriza, Santos E.; Cheng, Bin; Wang, Daniel Y.; Truong, Wanda; Spotnitz, Henry M.

    2017-01-01

    Objective Post-cardiopulmonary bypass biventricular pacing improves hemodynamics but without clearly defined predictors of response. Based on preclinical studies and prior observations, it was suspected that diastolic dysfunction or pulmonary hypertension is predictive of hemodynamic benefit. Design Randomized controlled study of temporary biventricular pacing after cardiopulmonary bypass. Setting Single-center study at university-affiliated tertiary care hospital. Interventions Patients who underwent bypass with pre-operative ejection fraction ≤40% and QRS duration ≥100 ms or double-valve surgery were enrolled. At 3 time points between separation from bypass and postoperative day 1, pacing delays were varied to optimize hemodynamics. Participants Data from 43 patients were analyzed. Measurements and Main Results Cardiac output and arterial pressure were measured under no pacing, atrial pacing, and biventricular pacing. Preoperative echocardiograms and pulmonary artery catheterizations were reviewed, and measures of both systolic and diastolic function were compared to hemodynamic response. Early after separation, improvement in cardiac output was positively correlated with pulmonary vascular resistance (R2 = 0.97, p < 0.001), ventricle wall thickness (R2 = 0.72, p = 0.002)), and E/e′, a measure of abnormal diastolic ventricular filling velocity (R2 = 0.56, p = 0.04). Similar trends were seen with mean arterial pressure. QRS duration and ejection fraction did not correlate significantly with improvements in hemodynamics. Conclusions There may be an effect of biventricular pacing related to amelioration of abnormal diastolic filling patterns rather than electrical resynchronization in the postoperative state. PMID:25998068

  11. Nonpathologizing trauma interventions in abnormal psychology courses.

    PubMed

    Hoover, Stephanie M; Luchner, Andrew F; Pickett, Rachel F

    2016-01-01

    Because abnormal psychology courses presuppose a focus on pathological human functioning, nonpathologizing interventions within these classes are particularly powerful and can reach survivors, bystanders, and perpetrators. Interventions are needed to improve the social response to trauma on college campuses. By applying psychodynamic and feminist multicultural theory, instructors can deliver nonpathologizing interventions about trauma and trauma response within these classes. We recommend class-based interventions with the following aims: (a) intentionally using nonpathologizing language, (b) normalizing trauma responses, (c) subjectively defining trauma, (d) challenging secondary victimization, and (e) questioning the delineation of abnormal and normal. The recommendations promote implications for instructor self-reflection, therapy interventions, and future research.

  12. Neural responses to sounds presented on and off the beat of ecologically valid music

    PubMed Central

    Tierney, Adam; Kraus, Nina

    2013-01-01

    The tracking of rhythmic structure is a vital component of speech and music perception. It is known that sequences of identical sounds can give rise to the percept of alternating strong and weak sounds, and that this percept is linked to enhanced cortical and oscillatory responses. The neural correlates of the perception of rhythm elicited by ecologically valid, complex stimuli, however, remain unexplored. Here we report the effects of a stimulus' alignment with the beat on the brain's processing of sound. Human subjects listened to short popular music pieces while simultaneously hearing a target sound. Cortical and brainstem electrophysiological onset responses to the sound were enhanced when it was presented on the beat of the music, as opposed to shifted away from it. Moreover, the size of the effect of alignment with the beat on the cortical response correlated strongly with the ability to tap to a beat, suggesting that the ability to synchronize to the beat of simple isochronous stimuli and the ability to track the beat of complex, ecologically valid stimuli may rely on overlapping neural resources. These results suggest that the perception of musical rhythm may have robust effects on processing throughout the auditory system. PMID:23717268

  13. Cognitive control dysfunction and abnormal frontal cortex activation in stimulant drug users and their biological siblings.

    PubMed

    Smith, D G; Jones, P S; Bullmore, E T; Robbins, T W; Ersche, K D

    2013-05-14

    Cognitive and neural abnormalities are known to accompany chronic drug abuse, with impairments in cognition and changes in cortical structure seen in stimulant-dependent individuals. However, premorbid differences have also been observed in the brains and behavior of individuals at risk for substance abuse, before they develop dependence. Endophenotype research has emerged as a useful method for assessing preclinical traits that may be risk factors for pathology by studying patient populations and their undiagnosed first-degree relatives. This study used the color-word Stroop task to assess executive functioning in stimulant-dependent individuals, their unaffected biological siblings and unrelated healthy control volunteers using a functional magnetic resonance imaging paradigm. Both the stimulant-dependent and sibling participants demonstrated impairments in cognitive control and processing speed on the task, registering significantly longer response latencies. However, the two groups generated very different neural responses, with the sibling participants exhibiting a significant decrease in activation in the inferior frontal gyrus compared with both stimulant-dependent individuals and control participants. Both target groups also demonstrated a decrease in hemispheric laterality throughout the task, exhibiting a disproportionate increase in right hemispheric activation, which was associated with their behavioral inefficiencies. These findings not only suggest a possible risk factor for stimulant abuse of poor inhibitory control and cortical inefficiency but they also demonstrate possible adaptations in the brains of stimulant users.

  14. Branding and a child's brain: an fMRI study of neural responses to logos.

    PubMed

    Bruce, Amanda S; Bruce, Jared M; Black, William R; Lepping, Rebecca J; Henry, Janice M; Cherry, Joseph Bradley C; Martin, Laura E; Papa, Vlad B; Davis, Ann M; Brooks, William M; Savage, Cary R

    2014-01-01

    Branding and advertising have a powerful effect on both familiarity and preference for products, yet no neuroimaging studies have examined neural response to logos in children. Food advertising is particularly pervasive and effective in manipulating choices in children. The purpose of this study was to examine how healthy children's brains respond to common food and other logos. A pilot validation study was first conducted with 32 children to select the most culturally familiar logos, and to match food and non-food logos on valence and intensity. A new sample of 17 healthy weight children were then scanned using functional magnetic resonance imaging. Food logos compared to baseline were associated with increased activation in orbitofrontal cortex and inferior prefrontal cortex. Compared to non-food logos, food logos elicited increased activation in posterior cingulate cortex. Results confirmed that food logos activate some brain regions in children known to be associated with motivation. This marks the first study in children to examine brain responses to culturally familiar logos. Considering the pervasiveness of advertising, research should further investigate how children respond at the neural level to marketing.

  15. Predicting Response to Neoadjuvant Chemotherapy with PET Imaging Using Convolutional Neural Networks

    PubMed Central

    Ypsilantis, Petros-Pavlos; Siddique, Musib; Sohn, Hyon-Mok; Davies, Andrew; Cook, Gary; Goh, Vicky; Montana, Giovanni

    2015-01-01

    Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has become a standard component of diagnosis and staging in oncology, and is becoming more important as a quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient’s response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a “radiomics” approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra-tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models. PMID:26355298

  16. A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and roadmap for future research

    PubMed Central

    Phillips, Mary L; Swartz, Holly A.

    2014-01-01

    Objective This critical review appraises neuroimaging findings in bipolar disorder in emotion processing, emotion regulation, and reward processing neural circuitry, to synthesize current knowledge of the neural underpinnings of bipolar disorder, and provide a neuroimaging research “roadmap” for future studies. Method We examined findings from all major studies in bipolar disorder that used fMRI, volumetric analyses, diffusion imaging, and resting state techniques, to inform current conceptual models of larger-scale neural circuitry abnormalities in bipolar disorder Results Bipolar disorder can be conceptualized in neural circuitry terms as parallel dysfunction in bilateral prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion processing and emotion regulation neural circuitries, together with an “overactive” left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward processing circuitry, that result in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation and heightened reward sensitivity. A potential structural basis for these functional abnormalities are gray matter decreases in prefrontal and temporal cortices, amygdala and hippocampus, and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Conclusion Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuitries supporting emotion processing, emotion regulation and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in bipolar disorder and at-risk youth; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful, individual

  17. [Cognitive abnormalities and cannabis use].

    PubMed

    Solowij, Nadia; Pesa, Nicole

    2010-05-01

    Evidence that cannabis use impairs cognitive function in humans has been accumulating in recent decades. The purpose of this overview is to update knowledge in this area with new findings from the most recent literature. Literature searches were conducted using the Web of Science database up to February 2010. The terms searched were: "cannabi*" or "marijuana", and "cogniti*" or "memory" or "attention" or "executive function", and human studies were reviewed preferentially over the animal literature. Cannabis use impairs memory, attention, inhibitory control, executive functions and decision making, both during the period of acute intoxication and beyond, persisting for hours, days, weeks or more after the last use of cannabis. Pharmacological challenge studies in humans are elucidating the nature and neural substrates of cognitive changes associated with various cannabinoids. Long-term or heavy cannabis use appears to result in longer-lasting cognitive abnormalities and possibly structural brain alterations. Greater adverse cognitive effects are associated with cannabis use commencing in early adolescence. The endogenous cannabinoid system is involved in regulatory neural mechanisms that modulate processes underlying a range of cognitive functions that are impaired by cannabis. Deficits in human users most likely therefore reflect neuroadaptations and altered functioning of the endogenous cannabinoid system.

  18. Musical training shapes neural responses to melodic and prosodic expectation.

    PubMed

    Zioga, Ioanna; Di Bernardi Luft, Caroline; Bhattacharya, Joydeep

    2016-11-01

    Current research on music processing and syntax or semantics in language suggests that music and language share partially overlapping neural resources. Pitch also constitutes a common denominator, forming melody in music and prosody in language. Further, pitch perception is modulated by musical training. The present study investigated how music and language interact on pitch dimension and whether musical training plays a role in this interaction. For this purpose, we used melodies ending on an expected or unexpected note (melodic expectancy being estimated by a computational model) paired with prosodic utterances which were either expected (statements with falling pitch) or relatively unexpected (questions with rising pitch). Participants' (22 musicians, 20 nonmusicians) ERPs and behavioural responses in a statement/question discrimination task were recorded. Participants were faster for simultaneous expectancy violations in the melodic and linguistic stimuli. Further, musicians performed better than nonmusicians, which may be related to their increased pitch tracking ability. At the neural level, prosodic violations elicited a front-central positive ERP around 150ms after the onset of the last word/note, while musicians presented reduced P600 in response to strong incongruities (questions on low-probability notes). Critically, musicians' P800 amplitudes were proportional to their level of musical training, suggesting that expertise might shape the pitch processing of language. The beneficial aspect of expertise could be attributed to its strengthening effect of general executive functions. These findings offer novel contributions to our understanding of shared higher-order mechanisms between music and language processing on pitch dimension, and further demonstrate a potential modulation by musical expertise. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Neural Correlates of the Binaural Masking Level Difference in Human Frequency-Following Responses.

    PubMed

    Clinard, Christopher G; Hodgson, Sarah L; Scherer, Mary Ellen

    2017-04-01

    The binaural masking level difference (BMLD) is an auditory phenomenon where binaural tone-in-noise detection is improved when the phase of either signal or noise is inverted in one of the ears (S π N o or S o N π , respectively), relative to detection when signal and noise are in identical phase at each ear (S o N o ). Processing related to BMLDs and interaural time differences has been confirmed in the auditory brainstem of non-human mammals; in the human auditory brainstem, phase-locked neural responses elicited by BMLD stimuli have not been systematically examined across signal-to-noise ratio. Behavioral and physiological testing was performed in three binaural stimulus conditions: S o N o , S π N o , and S o N π . BMLDs at 500 Hz were obtained from 14 young, normal-hearing adults (ages 21-26). Physiological BMLDs used the frequency-following response (FFR), a scalp-recorded auditory evoked potential dependent on sustained phase-locked neural activity; FFR tone-in-noise detection thresholds were used to calculate physiological BMLDs. FFR BMLDs were significantly smaller (poorer) than behavioral BMLDs, and FFR BMLDs did not reflect a physiological release from masking, on average. Raw FFR amplitude showed substantial reductions in the S π N o condition relative to S o N o and S o N π conditions, consistent with negative effects of phase summation from left and right ear FFRs. FFR amplitude differences between stimulus conditions (e.g., S o N o amplitude-S π N o amplitude) were significantly predictive of behavioral S π N o BMLDs; individuals with larger amplitude differences had larger (better) behavioral B MLDs and individuals with smaller amplitude differences had smaller (poorer) behavioral B MLDs. These data indicate a role for sustained phase-locked neural activity in BMLDs of humans and are the first to show predictive relationships between behavioral BMLDs and human brainstem responses.

  20. Reciprocal neural response within lateral and ventral medial prefrontal cortex during hot and cold reasoning.

    PubMed

    Goel, Vinod; Dolan, Raymond J

    2003-12-01

    Logic is widely considered the basis of rationality. Logical choices, however, are often influenced by emotional responses, sometimes to our detriment, sometimes to our advantage. To understand the neural basis of emotionally neutral ("cold") and emotionally salient ("hot") reasoning we studied 19 volunteers using event-related fMRI, as they made logical judgments about arguments that varied in emotional saliency. Despite identical logical form and content categories across "hot" and "cold" reasoning conditions, lateral and ventral medial prefrontal cortex showed reciprocal response patterns as a function of emotional saliency of content. "Cold" reasoning trials resulted in enhanced activity in lateral/dorsal lateral prefrontal cortex (L/DLPFC) and suppression of activity in ventral medial prefrontal cortex (VMPFC). By contrast, "hot" reasoning trials resulted in enhanced activation in VMPFC and suppression of activation in L/DLPFC. This reciprocal engagement of L/DLPFC and VMPFC provides evidence for a dynamic neural system for reasoning, the configuration of which is strongly influenced by emotional saliency.

  1. Quantitative Nucleotide Level Analysis of Regulation of Translation in Response to Depolarization of Cultured Neural Cells

    PubMed Central

    Dalal, Jasbir S.; Yang, Chengran; Sapkota, Darshan; Lake, Allison M.; O'Brien, David R.; Dougherty, Joseph D.

    2017-01-01

    Studies on regulation of gene expression have contributed substantially to understanding mechanisms for the long-term activity-dependent alterations in neural connectivity that are thought to mediate learning and memory. Most of these studies, however, have focused on the regulation of mRNA transcription. Here, we utilized high-throughput sequencing coupled with ribosome footprinting to globally characterize the regulation of translation in primary mixed neuronal-glial cultures in response to sustained depolarization. We identified substantial and complex regulation of translation, with many transcripts demonstrating changes in ribosomal occupancy independent of transcriptional changes. We also examined sequence-based mechanisms that might regulate changes in translation in response to depolarization. We found that these are partially mediated by features in the mRNA sequence—notably upstream open reading frames and secondary structure in the 5′ untranslated region—both of which predict downregulation in response to depolarization. Translationally regulated transcripts are also more likely to be targets of FMRP and include genes implicated in autism in humans. Our findings support the idea that control of mRNA translation plays an important role in response to neural activity across the genome. PMID:28190998

  2. Neural Activation during Inhibition Predicts Initiation of Substance Use in Adolescence

    PubMed Central

    Norman, Andria L.; Pulido, Carmen; Squeglia, Lindsay M.; Spadoni, Andrea D.; Paulus, Martin P.; Tapert, Susan F.

    2011-01-01

    Background Problems inhibiting non-adaptive behaviors have been linked to an increased risk for substance use and other risk taking behaviors in adolescence. This study examines the hypothesis that abnormalities in neural activation during inhibition in early adolescence may predict subsequent substance involvement. Methods Thirty eight adolescents from local area middle schools, ages 12–14, with very limited histories of substance use, underwent functional magnetic resonance imaging (fMRI) as they performed a go/no-go task of response inhibition and response selection. Adolescents and their parents were then followed annually with interviews covering substance use and other behaviors. Based on follow-up data, youth were classified as transitioning to heavy use of alcohol (TU; n=21), or as healthy controls (CON; n=17). Results At baseline, prior to the onset of use, youth who later transitioned into heavy use of alcohol showed significantly less activation than those who went on to remain non to minimal users throughout adolescence. Activation reductions in TU at baseline were seen on no-go trials in 12 brain regions, including right inferior frontal gyrus, left dorsal and medial frontal areas, bilateral motor cortex, cingulate gyrus, left putamen, bilateral middle temporal gyri, and bilateral inferior parietal lobules (corrected p < .01, each cluster ≥ 32 contiguous voxels). Conclusions These results support the hypothesis that less neural activity during response inhibition demands predicts future involvement with problem behaviors such as alcohol and other substance use. PMID:21782354

  3. Fetal karyotyping for chromosome abnormalities after an unexplained elevated maternal serum alpha-fetoprotein screening.

    PubMed

    Feuchtbaum, L B; Cunningham, G; Waller, D K; Lustig, L S; Tompkinson, D G; Hook, E B

    1995-08-01

    To study the chromosome abnormality rate among women with elevated levels of maternal serum alpha-fetoprotein (MSAFP) and the types of chromosome abnormalities in this population, and to compare this rate with reports in the literature and the rate observed in the general population. We studied 8097 women who chose to undergo amniocentesis and fetal karyotyping after having an elevated MSAFP test of 2.5 multiples of the median (MOM) or higher. All abnormal karyotypes were reviewed and grouped according to whether the elevated MSAFP value could be explained by a ventral wall or neural tube defect. The overall chromosome abnormality rate was 13.83 per 1000 amniocenteses. The rate in the "unexplained" group was 10.92 per 1000 amniocenteses. Just over half (53%) of the abnormal karyotypes were autosomal anomalies, and 47% were sex chromosome abnormalities. The autosomal aneuploidies observed most frequently were triploidy and trisomy 13. The sex chromosome abnormalities observed most frequently were the XXY and XYY karyotypes. Women who have unexplained elevated MSAFP values of 2.5 MOM or greater have a twofold increase in the rate of chromosome abnormalities in their fetuses compared with the general population (P < or = .001). This rate is consistent with other studies that used a 2.5 MOM cutoff. Studies that used a 2.0 MOM cutoff have reported chromosome abnormality rates that do not vary from general population estimates.

  4. T1r3 taste receptor involvement in gustatory neural responses to ethanol and oral ethanol preference.

    PubMed

    Brasser, Susan M; Norman, Meghan B; Lemon, Christian H

    2010-05-01

    Elevated alcohol consumption is associated with enhanced preference for sweet substances across species and may be mediated by oral alcohol-induced activation of neurobiological substrates for sweet taste. Here, we directly examined the contribution of the T1r3 receptor protein, important for sweet taste detection in mammals, to ethanol intake and preference and the neural processing of ethanol taste by measuring behavioral and central neurophysiological responses to oral alcohol in T1r3 receptor-deficient mice and their C57BL/6J background strain. T1r3 knockout and wild-type mice were tested in behavioral preference assays for long-term voluntary intake of a broad concentration range of ethanol, sucrose, and quinine. For neurophysiological experiments, separate groups of mice of each genotype were anesthetized, and taste responses to ethanol and stimuli of different taste qualities were electrophysiologically recorded from gustatory neurons in the nucleus of the solitary tract. Mice lacking the T1r3 receptor were behaviorally indifferent to alcohol (i.e., ∼50% preference values) at concentrations typically preferred by wild-type mice (5-15%). Central neural taste responses to ethanol in T1r3-deficient mice were significantly lower compared with C57BL/6J controls, a strain for which oral ethanol stimulation produced a concentration-dependent activation of sweet-responsive NTS gustatory neurons. An attenuated difference in ethanol preference between knockouts and controls at concentrations >15% indicated that other sensory and/or postingestive effects of ethanol compete with sweet taste input at high concentrations. As expected, T1r3 knockouts exhibited strongly suppressed behavioral and neural taste responses to sweeteners but did not differ from wild-type mice in responses to prototypic salt, acid, or bitter stimuli. These data implicate the T1r3 receptor in the sensory detection and transduction of ethanol taste.

  5. Gestational naltrexone ameliorates fetal ethanol exposures enhancing effect on the postnatal behavioral and neural response to ethanol

    PubMed Central

    Youngentob, Steven L; Kent, Paul F; Youngentob, Lisa M

    2012-01-01

    The association between gestational exposure to ethanol and adolescent ethanol abuse is well established. Recent animal studies support the role of fetal ethanol experience-induced chemosensory plasticity as contributing to this observation. Previously, we established that fetal ethanol exposure, delivered through a dam’s diet throughout gestation, tuned the neural response of the peripheral olfactory system of early postnatal rats to the odor of ethanol. This occurred in conjunction with a loss of responsiveness to other odorants. The instinctive behavioral response to the odor of ethanol was also enhanced. Importantly, there was a significant contributory link between the altered response to the odor of ethanol and increased ethanol avidity when assessed in the same animals. Here, we tested whether the neural and behavioral olfactory plasticity, and their relationship to enhanced ethanol intake, is a result of the mere exposure to ethanol or whether it requires the animal to associate ethanol’s reinforcing properties with its odor attributes. In this later respect, the opioid system is important in the mediation (or modulation) of the reinforcing aspects of ethanol. To block endogenous opiates during prenatal life, pregnant rats received daily intraperitoneal administration of the opiate antagonist naltrexone from gestational day 6–21 jointly with ethanol delivered via diet. Relative to control progeny, we found that gestational exposure to naltrexone ameliorated the enhanced postnatal behavioral response to the odor of ethanol and postnatal drug avidity. Our findings support the proposition that in utero ethanol-induced olfactory plasticity (and its relationship to postnatal intake) requires, at least in part, the associative pairing between ethanol’s odor quality and its reinforcing aspects. We also found suggestive evidence that fetal naltrexone ameliorated the untoward effects of gestational ethanol exposure on the neural response to non

  6. The relationship of abnormal foot pronation to hallux abducto valgus--a pilot study.

    PubMed

    Ross, F D

    1986-08-01

    Abnormal foot mechanics is the most common cause of hallux abducto valgus. To date no quantitative data regarding the relationship between abnormal foot mechanics and the degree of hallux abducto valgus has been presented. An outline of the abnormal foot mechanics responsible for hallux abducto valgus is described along with a technique for measuring the extent of abnormal function. A common intrinsic abnormality responsible for hallux abducto valgus is described along with its diagnosis and orthotic treatment.

  7. Altruistic and self-serving goals modulate behavioral and neural responses in deception

    PubMed Central

    Wu, Song; Wu, Haiyan; Wang, Chengyao; Jiao, Can; Luo, Yuejia

    2018-01-01

    Abstract People tell lies not only for their own self-interests but sometimes also to help others. Little is known about the ways in which different types of goals modulate behaviors and neural responses in deception. The present study investigated the neural processes associated with spontaneous deception that occurs with altruistic reasons (i.e. the money would be donated to charity), self-serving reasons (i.e. the participant receives all of the money) and mixed goals (i.e. the money would be equally split between the participant and the charity). Altruistic motivation for deception reduced the intensity of moral conflict and the subsequent mental cost of resolving this conflict, reflected by a smaller N2–P3 effect in the purely altruistic condition. When making decisions about whether to lie, self-interest was a stronger motivator than others’ interests, and the participants tended to lie more for themselves than for others. When the lie could be mutually beneficial for both of the self and others, the participants tended to lie even when they knew that they could be easily caught, but they actually lied for their own self-interest rather than for altruistic reasons. These findings shed light on the neural basis of ‘good lies’ and decision-making in mutually beneficial situations. PMID:29149322

  8. Neural response to pictorial health warning labels can predict smoking behavioral change.

    PubMed

    Riddle, Philip J; Newman-Norlund, Roger D; Baer, Jessica; Thrasher, James F

    2016-11-01

    In order to improve our understanding of how pictorial health warning labels (HWLs) influence smoking behavior, we examined whether brain activity helps to explain smoking behavior above and beyond self-reported effectiveness of HWLs. We measured the neural response in the ventromedial prefrontal cortex (vmPFC) and the amygdala while adult smokers viewed HWLs. Two weeks later, participants' self-reported smoking behavior and biomarkers of smoking behavior were reassessed. We compared multiple models predicting change in self-reported smoking behavior (cigarettes per day [CPD]) and change in a biomarkers of smoke exposure (expired carbon monoxide [CO]). Brain activity in the vmPFC and amygdala not only predicted changes in CO, but also accounted for outcome variance above and beyond self-report data. Neural data were most useful in predicting behavioral change as quantified by the objective biomarker (CO). This pattern of activity was significantly modulated by individuals' intention to quit. The finding that both cognitive (vmPFC) and affective (amygdala) brain areas contributed to these models supports the idea that smokers respond to HWLs in a cognitive-affective manner. Based on our findings, researchers may wish to consider using neural data from both cognitive and affective networks when attempting to predict behavioral change in certain populations (e.g. cigarette smokers). © The Author (2016). Published by Oxford University Press.

  9. Abnormal functional connectivity during visuospatial processing is associated with disrupted organisation of white matter in autism

    PubMed Central

    McGrath, Jane; Johnson, Katherine; O'Hanlon, Erik; Garavan, Hugh; Leemans, Alexander; Gallagher, Louise

    2013-01-01

    Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD. PMID:24133425

  10. The effect of verbal context on olfactory neural responses.

    PubMed

    Bensafi, Moustafa; Croy, Ilona; Phillips, Nicola; Rouby, Catherine; Sezille, Caroline; Gerber, Johannes; Small, Dana M; Hummel, Thomas

    2014-03-01

    Odor names refer usually to "source" object categories. For example, the smell of rose is often described with its source category (flower). However, linguistic studies suggest that odors can also be named with labels referring to categories of "practices". This is the case when rose odor is described with a verbal label referring to its use in fragrance practices ("body lotion," cosmetic for example). It remains unknown whether naming an odor by its practice category influences olfactory neural responses differently than that observed when named with its source category. The aim of this study was to investigate this question. To this end, functional MRI was used in a within-subjects design comparing brain responses to four different odors (peach, chocolate, linden blossom, and rose) under two conditions whereby smells were described either (1) with their source category label (food and flower) or (2) with a practice category label (body lotion). Both types of labels induced activations in secondary olfactory areas (orbitofrontal cortex), whereas only the source label condition induced activation in the cingulate cortex and the insula. In summary, our findings offer a new look at olfactory perception by indicating differential brain responses depending on whether odors are named according to their source or practice category. Copyright © 2012 Wiley Periodicals, Inc.

  11. Mesodermal expression of integrin α5β1 regulates neural crest development and cardiovascular morphogenesis

    PubMed Central

    Liang, Dong; Wang, Xia; Mittal, Ashok; Dhiman, Sonam; Hou, Shuan-Yu; Degenhardt, Karl; Astrof, Sophie

    2014-01-01

    Integrin α5-null embryos die in mid-gestation from severe defects in cardiovascular morphogenesis, which stem from defective development of the neural crest, heart and vasculature. To investigate the role of integrin α5β1 in cardiovascular development, we used the Mesp1Cre knock-in strain of mice to ablate integrin α5 in the anterior mesoderm, which gives rise to all of the cardiac and many of the vascular and muscle lineages in the anterior portion of the embryo. Surprisingly, we found that mutant embryos displayed numerous defects related to the abnormal development of the neural crest such as cleft palate, ventricular septal defect, abnormal development of hypoglossal nerves, and defective remodeling of the aortic arch arteries. We found that defects in arch artery remodeling stem from the role of mesodermal integrin α5β1 in neural crest proliferation and differentiation into vascular smooth muscle cells, while proliferation of pharyngeal mesoderm and differentiation of mesodermal derivatives into vascular smooth muscle cells was not defective. Taken together our studies demonstrate a requisite role for mesodermal integrin α5β1 in signaling between the mesoderm and the neural crest, thereby regulating neural crest-dependent morphogenesis of essential embryonic structures. PMID:25242040

  12. Normal and abnormal human vestibular ocular function

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.

    1986-01-01

    The major motivation of this research is to understand the role the vestibular system plays in sensorimotor interactions which result in spatial disorientation and motion sickness. A second goal was to explore the range of abnormality as it is reflected in quantitative measures of vestibular reflex responses. The results of a study of vestibular reflex measurements in normal subjects and preliminary results in abnormal subjects are presented in this report. Statistical methods were used to define the range of normal responses, and determine age related changes in function.

  13. Interpretations of Frequency Domain Analyses of Neural Entrainment: Periodicity, Fundamental Frequency, and Harmonics.

    PubMed

    Zhou, Hong; Melloni, Lucia; Poeppel, David; Ding, Nai

    2016-01-01

    Brain activity can follow the rhythms of dynamic sensory stimuli, such as speech and music, a phenomenon called neural entrainment. It has been hypothesized that low-frequency neural entrainment in the neural delta and theta bands provides a potential mechanism to represent and integrate temporal information. Low-frequency neural entrainment is often studied using periodically changing stimuli and is analyzed in the frequency domain using the Fourier analysis. The Fourier analysis decomposes a periodic signal into harmonically related sinusoids. However, it is not intuitive how these harmonically related components are related to the response waveform. Here, we explain the interpretation of response harmonics, with a special focus on very low-frequency neural entrainment near 1 Hz. It is illustrated why neural responses repeating at f Hz do not necessarily generate any neural response at f Hz in the Fourier spectrum. A strong neural response at f Hz indicates that the time scales of the neural response waveform within each cycle match the time scales of the stimulus rhythm. Therefore, neural entrainment at very low frequency implies not only that the neural response repeats at f Hz but also that each period of the neural response is a slow wave matching the time scale of a f Hz sinusoid.

  14. Speech Evoked Auditory Brainstem Response in Stuttering

    PubMed Central

    Tahaei, Ali Akbar; Ashayeri, Hassan; Pourbakht, Akram; Kamali, Mohammad

    2014-01-01

    Auditory processing deficits have been hypothesized as an underlying mechanism for stuttering. Previous studies have demonstrated abnormal responses in subjects with persistent developmental stuttering (PDS) at the higher level of the central auditory system using speech stimuli. Recently, the potential usefulness of speech evoked auditory brainstem responses in central auditory processing disorders has been emphasized. The current study used the speech evoked ABR to investigate the hypothesis that subjects with PDS have specific auditory perceptual dysfunction. Objectives. To determine whether brainstem responses to speech stimuli differ between PDS subjects and normal fluent speakers. Methods. Twenty-five subjects with PDS participated in this study. The speech-ABRs were elicited by the 5-formant synthesized syllable/da/, with duration of 40 ms. Results. There were significant group differences for the onset and offset transient peaks. Subjects with PDS had longer latencies for the onset and offset peaks relative to the control group. Conclusions. Subjects with PDS showed a deficient neural timing in the early stages of the auditory pathway consistent with temporal processing deficits and their abnormal timing may underlie to their disfluency. PMID:25215262

  15. Levetiracetam reduces abnormal network activations in temporal lobe epilepsy.

    PubMed

    Wandschneider, Britta; Stretton, Jason; Sidhu, Meneka; Centeno, Maria; Kozák, Lajos R; Symms, Mark; Thompson, Pamela J; Duncan, John S; Koepp, Matthias J

    2014-10-21

    We used functional MRI (fMRI) and a left-lateralizing verbal and a right-lateralizing visual-spatial working memory (WM) paradigm to investigate the effects of levetiracetam (LEV) on cognitive network activations in patients with drug-resistant temporal lobe epilepsy (TLE). In a retrospective study, we compared task-related fMRI activations and deactivations in 53 patients with left and 54 patients with right TLE treated with (59) or without (48) LEV. In patients on LEV, activation patterns were correlated with the daily LEV dose. We isolated task- and syndrome-specific effects. Patients on LEV showed normalization of functional network deactivations in the right temporal lobe in right TLE during the right-lateralizing visual-spatial task and in the left temporal lobe in left TLE during the verbal task. In a post hoc analysis, a significant dose-dependent effect was demonstrated in right TLE during the visual-spatial WM task: the lower the LEV dose, the greater the abnormal right hippocampal activation. At a less stringent threshold (p < 0.05, uncorrected for multiple comparisons), a similar dose effect was observed in left TLE during the verbal task: both hippocampi were more abnormally activated in patients with lower doses, but more prominently on the left. Our findings suggest that LEV is associated with restoration of normal activation patterns. Longitudinal studies are necessary to establish whether the neural patterns translate to drug response. This study provides Class III evidence that in patients with drug-resistant TLE, levetiracetam has a dose-dependent facilitation of deactivation of mesial temporal structures. © 2014 American Academy of Neurology.

  16. Abnormal processing of deontological guilt in obsessive-compulsive disorder.

    PubMed

    Basile, Barbara; Mancini, Francesco; Macaluso, Emiliano; Caltagirone, Carlo; Bozzali, Marco

    2014-07-01

    Guilt plays a significant role in the occurrence and maintenance of obsessive-compulsive disorder (OCD). Two major types of guilt have been identified: one deriving from the transgression of a moral rule (deontological guilt DG), another (altruistic guilt AG), relying on the assumption of having compromised a personal altruistic goal. Clinical evidence suggests that OCD patients are particularly sensitive to DG, but not AG. In this functional magnetic resonance imaging (fMRI) study, we investigated brain response of OCD patients while processing DG and AG stimuli. A previously validated fMRI paradigm was used to selectively evoke DG and AG, and anger and sadness, as control emotions in 13 OCD patients and 19 healthy controls. Patients' behavioral results showed a prominent attitude to experience guilt, compared to controls, while accomplishing task. fMRI results revealed that patients have reduced activation in the anterior cingulate (ACC) and frontal gyrus when experiencing guilt, regardless of its specific type (DG or AG). When separately considering each type of guilt (against each of its control), patients showed decreased activation in the ACC, the insula and the precuneus, for DG. No significant differences were observed between groups when processing AG, anger or sad stimuli. This study provides evidence for an abnormal processing of guilt, and specifically DG, in OCD patients. We suggest that decreased activation may reflect patients' cerebral efficiency, which derives from their frequent exposure to guilty feelings ("neural efficiency hypothesis"). In conclusion, our study confirms a selective abnormal processing of guilt, and specifically DG, in OCD.

  17. Directional abnormalities of vestibular and optokinetic responses in cerebellar disease

    NASA Technical Reports Server (NTRS)

    Walker, M. F.; Zee, D. S.; Shelhamer, M. J. (Principal Investigator)

    1999-01-01

    Directional abnormalities of vestibular and optokinetic responses in patients with cerebellar degeneration are reported. Three-axis magnetic search-coil recordings of the eye and head were performed in eight cerebellar patients. Among these patients, examples of directional cross-coupling were found during (1) high-frequency, high-acceleration head thrusts; (2) constant-velocity chair rotations with the head fixed; (3) constant-velocity optokinetic stimulation; and (4) following repetitive head shaking. Cross-coupling during horizontal head thrusts consisted of an inappropriate upward eye-velocity component. In some patients, sustained constant-velocity yaw-axis chair rotations produced a mixed horizontal-torsional nystagmus and/or an increase in the baseline vertical slow-phase velocity. Following horizontal head shaking, some patients showed an increase in the slow-phase velocity of their downbeat nystagmus. These various forms of cross-coupling did not necessarily occur to the same degree in a given patient; this suggests that different mechanisms may be responsible. It is suggested that cross-coupling during head thrusts may reflect a loss of calibration of brainstem connections involved in the direct vestibular pathways, perhaps due to dysfunction of the flocculus. Cross-coupling during constant-velocity rotations and following head shaking may result from a misorientation of the angular eye-velocity vector in the velocity-storage system. Finally, responses to horizontal optokinetic stimulation included an inappropriate torsional component in some patients. This suggests that the underlying organization of horizontal optokinetic tracking is in labyrinthine coordinates. The findings are also consistent with prior animal-lesion studies that have shown a role for the vestibulocerebellum in the control of the direction of the VOR.

  18. Pdgfrα functions in endothelial-derived cells to regulate neural crest cells and the development of the great arteries.

    PubMed

    Aghajanian, Haig; Cho, Young Kuk; Rizer, Nicholas W; Wang, Qiaohong; Li, Li; Degenhardt, Karl; Jain, Rajan

    2017-09-01

    Originating as a single vessel emerging from the embryonic heart, the truncus arteriosus must septate and remodel into the aorta and pulmonary artery to support postnatal life. Defective remodeling or septation leads to abnormalities collectively known as conotruncal defects, which are associated with significant mortality and morbidity. Multiple populations of cells must interact to coordinate outflow tract remodeling, and the cardiac neural crest has emerged as particularly important during this process. Abnormalities in the cardiac neural crest have been implicated in the pathogenesis of multiple conotruncal defects, including persistent truncus arteriosus, double outlet right ventricle and tetralogy of Fallot. However, the role of the neural crest in the pathogenesis of another conotruncal abnormality, transposition of the great arteries, is less well understood. In this report, we demonstrate an unexpected role of Pdgfra in endothelial cells and their derivatives during outflow tract development. Loss of Pdgfra in endothelium and endothelial-derived cells results in double outlet right ventricle and transposition of the great arteries. Our data suggest that loss of Pdgfra in endothelial-derived mesenchyme in the outflow tract endocardial cushions leads to a secondary defect in neural crest migration during development. © 2017. Published by The Company of Biologists Ltd.

  19. Neural Events in the Reinforcement Contingency

    ERIC Educational Resources Information Center

    Silva, Maria Teresa Araujo; Goncalves, Fabio Leyser; Garcia-Mijares, Miriam

    2007-01-01

    When neural events are analyzed as stimuli and responses, functional relations among them and among overt stimuli and responses can be unveiled. The integration of neuroscience and the experimental analysis of behavior is beginning to provide empirical evidence of involvement of neural events in the three-term contingency relating discriminative…

  20. Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface

    NASA Astrophysics Data System (ADS)

    Ereifej, Evon S.

    Neural electrode devices hold great promise to help people with the restoration of lost functions, however, research is lacking in the biomaterial design of a stable, long-term device. Current devices lack long term functionality, most have been found unable to record neural activity within weeks after implantation due to the development of glial scar tissue (Polikov et al., 2006; Zhong and Bellamkonda, 2008). The long-term effect of chronically implanted electrodes is the formation of a glial scar made up of reactive astrocytes and the matrix proteins they generate (Polikov et al., 2005; Seil and Webster, 2008). Scarring is initiated when a device is inserted into brain tissue and is associated with an inflammatory response. Activated astrocytes are hypertrophic, hyperplastic, have an upregulation of intermediate filaments GFAP and vimentin expression, and filament formation (Buffo et al., 2010; Gervasi et al., 2008). Current approaches towards inhibiting the initiation of glial scarring range from altering the geometry, roughness, size, shape and materials of the device (Grill et al., 2009; Kotov et al., 2009; Kotzar et al., 2002; Szarowski et al., 2003). Literature has shown that surface topography modifications can alter cell alignment, adhesion, proliferation, migration, and gene expression (Agnew et al., 1983; Cogan et al., 2005; Cogan et al., 2006; Merrill et al., 2005). Thus, the goals of the presented work are to study the cellular response to biomaterials used in neural electrode fabrication and assess surface topography effects on minimizing astrogliosis. Initially, to examine astrocyte response to various materials used in neural electrode fabrication, astrocytes were cultured on platinum, silicon, PMMA, and SU-8 surfaces, with polystyrene as the control surface. Cell proliferation, viability, morphology and gene expression was measured for seven days in vitro. Results determined the cellular characteristics, reactions and growth rates of astrocytes

  1. Associations among Pubertal Development, Empathic Ability, and Neural Responses While Witnessing Peer Rejection in Adolescence

    ERIC Educational Resources Information Center

    Masten, Carrie L.; Eisenberger, Naomi I.; Pfeifer, Jennifer H.; Colich, Natalie L.; Dapretto, Mirella

    2013-01-01

    Links among concurrent and longitudinal changes in pubertal development and empathic ability from ages 10 to 13 and neural responses while witnessing peer rejection at age 13 were examined in 16 participants. More advanced pubertal development at age 13, and greater longitudinal increases in pubertal development, related to increased activity in…

  2. Unjoined primary and secondary neural tubes: junctional neural tube defect, a new form of spinal dysraphism caused by disturbance of junctional neurulation.

    PubMed

    Eibach, Sebastian; Moes, Greg; Hou, Yong Jin; Zovickian, John; Pang, Dachling

    2017-10-01

    Primary and secondary neurulation are the two known processes that form the central neuraxis of vertebrates. Human phenotypes of neural tube defects (NTDs) mostly fall into two corresponding categories consistent with the two types of developmental sequence: primary NTD features an open skin defect, an exposed, unclosed neural plate (hence an open neural tube defect, or ONTD), and an unformed or poorly formed secondary neural tube, and secondary NTD with no skin abnormality (hence a closed NTD) and a malformed conus caudal to a well-developed primary neural tube. We encountered three cases of a previously unrecorded form of spinal dysraphism in which the primary and secondary neural tubes are individually formed but are physically separated far apart and functionally disconnected from each other. One patient was operated on, in whom both the lumbosacral spinal cord from primary neurulation and the conus from secondary neurulation are each anatomically complete and endowed with functioning segmental motor roots tested by intraoperative triggered electromyography and direct spinal cord stimulation. The remarkable feature is that the two neural tubes are unjoined except by a functionally inert, probably non-neural band. The developmental error of this peculiar malformation probably occurs during the critical transition between the end of primary and the beginning of secondary neurulation, in a stage aptly called junctional neurulation. We describe the current knowledge concerning junctional neurulation and speculate on the embryogenesis of this new class of spinal dysraphism, which we call junctional neural tube defect.

  3. Individual differences in regulatory focus predict neural response to reward.

    PubMed

    Scult, Matthew A; Knodt, Annchen R; Hanson, Jamie L; Ryoo, Minyoung; Adcock, R Alison; Hariri, Ahmad R; Strauman, Timothy J

    2017-08-01

    Although goal pursuit is related to both functioning of the brain's reward circuits and psychological factors, the literatures surrounding these concepts have often been separate. Here, we use the psychological construct of regulatory focus to investigate individual differences in neural response to reward. Regulatory focus theory proposes two motivational orientations for personal goal pursuit: (1) promotion, associated with sensitivity to potential gain, and (2) prevention, associated with sensitivity to potential loss. The monetary incentive delay task was used to manipulate reward circuit function, along with instructional framing corresponding to promotion and prevention in a within-subject design. We observed that the more promotion oriented an individual was, the lower their ventral striatum response to gain cues. Follow-up analyses revealed that greater promotion orientation was associated with decreased ventral striatum response even to no-value cues, suggesting that promotion orientation may be associated with relatively hypoactive reward system function. The findings are also likely to represent an interaction between the cognitive and motivational characteristics of the promotion system with the task demands. Prevention orientation did not correlate with ventral striatum response to gain cues, supporting the discriminant validity of regulatory focus theory. The results highlight a dynamic association between individual differences in self-regulation and reward system function.

  4. Neural activation during response inhibition in adult Attention-Deficit/Hyperactivity Disorder: Preliminary findings on the effects of medication and symptom severity

    PubMed Central

    Congdon, Eliza; Altshuler, Lori L.; Mumford, Jeanette A.; Karlsgodt, Katherine H.; Sabb, Fred W.; Ventura, Joseph; McGough, James J.; London, Edythe D.; Cannon, Tyrone D.; Bilder, Robert M.; Poldrack, Russell A.

    2014-01-01

    Studies of adults with attention-deficit/hyperactivity disorder (ADHD) have suggested that they have deficient response inhibition, but findings concerning the neural correlates of inhibition in this patient population are inconsistent. We used the Stop-Signal task and functional magnetic resonance imaging (fMRI) to compare neural activation associated with response inhibition between adults with ADHD (N = 35) and healthy comparison subjects (N = 62), and in follow-up tests to examine the effect of current medication use and symptom severity. There were no differences in Stop-Signal task performance or neural activation between ADHD and control participants. Among the ADHD participants, however, significant differences were associated with current medication, with individuals taking psychostimulants (N = 25) showing less stopping-related activation than those not currently receiving psychostimulant medication (N = 10). Follow-up analyses suggested that this difference in activation was independent of symptom severity. These results provide evidence that deficits in inhibition-related neural activation persist in a subset of adult ADHD individuals, namely those individuals currently taking psychostimulants. These findings help to explain some of the disparities in the literature, and advance our understanding of why deficits in response inhibition are more variable in adult, as compared with child and adolescent, ADHD patients. PMID:24581734

  5. Neural activation during response inhibition in adult attention-deficit/hyperactivity disorder: preliminary findings on the effects of medication and symptom severity.

    PubMed

    Congdon, Eliza; Altshuler, Lori L; Mumford, Jeanette A; Karlsgodt, Katherine H; Sabb, Fred W; Ventura, Joseph; McGough, James J; London, Edythe D; Cannon, Tyrone D; Bilder, Robert M; Poldrack, Russell A

    2014-04-30

    Studies of adults with attention-deficit/hyperactivity disorder (ADHD) have suggested that they have deficient response inhibition, but findings concerning the neural correlates of inhibition in this patient population are inconsistent. We used the Stop-Signal task and functional magnetic resonance imaging (fMRI) to compare neural activation associated with response inhibition between adults with ADHD (N=35) and healthy comparison subjects (N=62), and in follow-up tests to examine the effect of current medication use and symptom severity. There were no differences in Stop-Signal task performance or neural activation between ADHD and control participants. Among the ADHD participants, however, significant differences were associated with current medication, with individuals taking psychostimulants (N=25) showing less stopping-related activation than those not currently receiving psychostimulant medication (N=10). Follow-up analyses suggested that this difference in activation was independent of symptom severity. These results provide evidence that deficits in inhibition-related neural activation persist in a subset of adult ADHD individuals, namely those individuals currently taking psychostimulants. These findings help to explain some of the disparities in the literature, and advance our understanding of why deficits in response inhibition are more variable in adult, as compared with child and adolescent, ADHD patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Dissociated emergent-response system and fine-processing system in human neural network and a heuristic neural architecture for autonomous humanoid robots.

    PubMed

    Yan, Xiaodan

    2010-01-01

    The current study investigated the functional connectivity of the primary sensory system with resting state fMRI and applied such knowledge into the design of the neural architecture of autonomous humanoid robots. Correlation and Granger causality analyses were utilized to reveal the functional connectivity patterns. Dissociation was within the primary sensory system, in that the olfactory cortex and the somatosensory cortex were strongly connected to the amygdala whereas the visual cortex and the auditory cortex were strongly connected with the frontal cortex. The posterior cingulate cortex (PCC) and the anterior cingulate cortex (ACC) were found to maintain constant communication with the primary sensory system, the frontal cortex, and the amygdala. Such neural architecture inspired the design of dissociated emergent-response system and fine-processing system in autonomous humanoid robots, with separate processing units and another consolidation center to coordinate the two systems. Such design can help autonomous robots to detect and respond quickly to danger, so as to maintain their sustainability and independence.

  7. Temporal lobe abnormalities in semantic processing by criminal psychopaths as revealed by functional magnetic resonance imaging.

    PubMed

    Kiehl, Kent A; Smith, Andra M; Mendrek, Adrianna; Forster, Bruce B; Hare, Robert D; Liddle, Peter F

    2004-04-30

    We tested the hypothesis that psychopathy is associated with abnormalities in semantic processing of linguistic information. Functional magnetic resonance imaging (fMRI) was used to elucidate and characterize the neural architecture underlying lexico-semantic processes in criminal psychopathic individuals and in a group of matched control participants. Participants performed a lexical decision task in which blocks of linguistic stimuli alternated with a resting baseline condition. In each lexical decision block, the stimuli were either concrete words and pseudowords or abstract words and pseudowords. Consistent with our hypothesis, psychopathic individuals, relative to controls, showed poorer behavioral performance for processing abstract words. Analysis of the fMRI data for both groups indicated that processing of word stimuli, compared with the resting baseline condition, was associated with neural activation in bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. Analyses confirmed our prediction that psychopathic individuals would fail to show the appropriate neural differentiation between abstract and concrete stimuli in the right anterior temporal gyrus and surrounding cortex. The results are consistent with other studies of semantic processing in psychopathy and support the theory that psychopathy is associated with right hemisphere abnormalities for processing conceptually abstract material.

  8. Temporal lobe abnormalities in semantic processing by criminal psychopaths as revealed by functional magnetic resonance imaging.

    PubMed

    Kiehl, Kent A; Smith, Andra M; Mendrek, Adrianna; Forster, Bruce B; Hare, Robert D; Liddle, Peter F

    2004-01-15

    We tested the hypothesis that psychopathy is associated with abnormalities in semantic processing of linguistic information. Functional magnetic resonance imaging (fMRI) was used to elucidate and characterize the neural architecture underlying lexico-semantic processes in criminal psychopathic individuals and in a group of matched control participants. Participants performed a lexical decision task in which blocks of linguistic stimuli alternated with a resting baseline condition. In each lexical decision block, the stimuli were either concrete words and pseudowords or abstract words and pseudowords. Consistent with our hypothesis, psychopathic individuals, relative to controls, showed poorer behavioral performance for processing abstract words. Analysis of the fMRI data for both groups indicated that processing of word stimuli, compared with the resting baseline condition, was associated with neural activation in bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. Analyses confirmed our prediction that psychopathic individuals would fail to show the appropriate neural differentiation between abstract and concrete stimuli in the right anterior temporal gyrus and surrounding cortex. The results are consistent with other studies of semantic processing in psychopathy and support the theory that psychopathy is associated with right hemisphere abnormalities for processing conceptually abstract material.

  9. How linear response shaped models of neural circuits and the quest for alternatives.

    PubMed

    Herfurth, Tim; Tchumatchenko, Tatjana

    2017-10-01

    In the past decades, many mathematical approaches to solve complex nonlinear systems in physics have been successfully applied to neuroscience. One of these tools is the concept of linear response functions. However, phenomena observed in the brain emerge from fundamentally nonlinear interactions and feedback loops rather than from a composition of linear filters. Here, we review the successes achieved by applying the linear response formalism to topics, such as rhythm generation and synchrony and by incorporating it into models that combine linear and nonlinear transformations. We also discuss the challenges encountered in the linear response applications and argue that new theoretical concepts are needed to tackle feedback loops and non-equilibrium dynamics which are experimentally observed in neural networks but are outside of the validity regime of the linear response formalism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Neural substrates of the impaired effort expenditure decision making in schizophrenia.

    PubMed

    Huang, Jia; Yang, Xin-Hua; Lan, Yong; Zhu, Cui-Ying; Liu, Xiao-Qun; Wang, Ye-Fei; Cheung, Eric F C; Xie, Guang-Rong; Chan, Raymond C K

    2016-09-01

    Unwillingness to expend more effort to pursue high value rewards has been associated with motivational anhedonia in schizophrenia (SCZ) and abnormal dopamine activity in the nucleus accumbens (NAcc). The authors hypothesized that dysfunction of the NAcc and the associated forebrain regions are involved in the impaired effort expenditure decision-making of SCZ. A 2 (reward magnitude: low vs. high) × 3 (probability: 20% vs. 50% vs. 80%) event-related fMRI design in the effort-expenditure for reward task (EEfRT) was used to examine the neural response of 23 SCZ patients and 23 demographically matched control participants when the participants made effort expenditure decisions to pursue uncertain rewards. SCZ patients were significantly less likely to expend high level of effort in the medium (50%) and high (80%) probability conditions than healthy controls. The neural response in the NAcc, the posterior cingulate gyrus and the left medial frontal gyrus in SCZ patients were weaker than healthy controls and did not linearly increase with an increase in reward magnitude and probability. Moreover, NAcc activity was positively correlated with the willingness to expend high-level effort and concrete consummatory pleasure experience. NAcc and posterior cingulate dysfunctions in SCZ patients may be involved in their impaired effort expenditure decision-making. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  11. NEURAL REACTIVITY TO REWARD AS A PREDICTOR OF COGNITIVE BEHAVIORAL THERAPY RESPONSE IN ANXIETY AND DEPRESSION.

    PubMed

    Burkhouse, Katie L; Kujawa, Autumn; Kennedy, Amy E; Shankman, Stewart A; Langenecker, Scott A; Phan, K Luan; Klumpp, Heide

    2016-04-01

    Cognitive behavioral therapy (CBT) is a well-established treatment for anxiety and depression; however, response to CBT is heterogeneous across patients and many remain symptomatic after therapy, raising the need to identify prospective predictors for treatment planning. Altered neural processing of reward has been implicated in both depression and anxiety, and improving hedonic capacity is a goal of CBT. However, little is known about how neural response to reward relates to CBT outcomes in depression and anxiety. The current study used the reward positivity (RewP) event-related potential (ERP) component to examine whether neural reactivity to reward would predict CBT response in a sample of patients with anxiety without depression (n = 30) and comorbid anxiety and depression (CAD, n = 22). Participants completed a guessing reward ERP paradigm before completing 12 weeks of standard CBT. The majority of the sample (68%; 35 out of 52 patients) responded to treatment, and those with a reduced RewP at baseline were more likely to respond to treatment. A reduced RewP was also associated with a greater pre-to-post CBT reduction in depressive symptoms among individuals with CAD, but not among individuals with pure anxiety. CBT may be most beneficial in reducing depressive symptoms for individuals who demonstrate decreased reward reactivity prior to treatment. CBT may target reward brain function, leading to greater improvement in symptoms. These effects may be strongest, and therefore most meaningful, for individuals with reward-processing deficits prior to treatment. © 2016 Wiley Periodicals, Inc.

  12. Neural Reactivity to Reward as a Predictor of Cognitive Behavioral Therapy Response in Anxiety and Depression

    PubMed Central

    Burkhouse, Katie L.; Kujawa, Autumn; Kennedy, Amy E.; Shankman, Stewart A.; Langenecker, Scott A.; Phan, K. Luan; Klumpp, Heide

    2016-01-01

    Background Cognitive behavioral therapy (CBT) is a well-established treatment for anxiety and depression; however, response to CBT is heterogeneous across patients and many remain symptomatic after therapy, raising the need to identify prospective predictors for treatment planning. Altered neural processing of reward has been implicated in both depression and anxiety, and improving hedonic capacity is a goal of CBT. However, little is known about how neural response to reward relates to CBT outcomes in depression and anxiety. The current study used the reward positivity (RewP) event-related potential (ERP) component to examine whether neural reactivity to reward would predict CBT response in a sample of patients with anxiety without depression (n = 30) and comorbid anxiety and depression (CAD, n = 22). Methods Participants completed a guessing reward ERP paradigm before completing 12 weeks of standard CBT. Results The majority of the sample (68%; 35 of 52 patients) responded to treatment, and those with a reduced RewP at baseline were more likely to respond to treatment. A reduced RewP was also associated with a greater pre-to-post CBT reduction in depressive symptoms among individuals with CAD, but not among individuals with pure anxiety. Conclusions CBT may be most beneficial in reducing depressive symptoms for individuals who demonstrate decreased reward reactivity prior to treatment. CBT may target reward brain function, leading to greater improvement in symptoms. These effects may be strongest, and therefore most meaningful, for individuals with reward processing deficits prior to treatment. PMID:27038409

  13. Neural entrainment to the rhythmic structure of music.

    PubMed

    Tierney, Adam; Kraus, Nina

    2015-02-01

    The neural resonance theory of musical meter explains musical beat tracking as the result of entrainment of neural oscillations to the beat frequency and its higher harmonics. This theory has gained empirical support from experiments using simple, abstract stimuli. However, to date there has been no empirical evidence for a role of neural entrainment in the perception of the beat of ecologically valid music. Here we presented participants with a single pop song with a superimposed bassoon sound. This stimulus was either lined up with the beat of the music or shifted away from the beat by 25% of the average interbeat interval. Both conditions elicited a neural response at the beat frequency. However, although the on-the-beat condition elicited a clear response at the first harmonic of the beat, this frequency was absent in the neural response to the off-the-beat condition. These results support a role for neural entrainment in tracking the metrical structure of real music and show that neural meter tracking can be disrupted by the presentation of contradictory rhythmic cues.

  14. Socioeconomic disadvantage and neural development from infancy through early childhood.

    PubMed

    Chin-Lun Hung, Galen; Hahn, Jill; Alamiri, Bibi; Buka, Stephen L; Goldstein, Jill M; Laird, Nan; Nelson, Charles A; Smoller, Jordan W; Gilman, Stephen E

    2015-12-01

    Early social experiences are believed to shape neurodevelopment, with potentially lifelong consequences. Yet minimal evidence exists regarding the role of the social environment on children's neural functioning, a core domain of neurodevelopment. We analysed data from 36 443 participants in the United States Collaborative Perinatal Project, a socioeconomically diverse pregnancy cohort conducted between 1959 and 1974. Study outcomes included: physician (neurologist or paediatrician)-rated neurological abnormality neonatally and thereafter at 4 months and 1 and 7 years; indicators of neurological hard signs and soft signs; and indicators of autonomic nervous system function. Children born to socioeconomically disadvantaged parents were more likely to exhibit neurological abnormalities at 4 months [odds ratio (OR) = 1.20; 95% confidence interval (CI) = 1.06, 1.37], 1 year (OR = 1.35; CI = 1.17, 1.56), and 7 years (OR = 1.67; CI = 1.48, 1.89), and more likely to exhibit neurological hard signs (OR = 1.39; CI = 1.10, 1.76), soft signs (OR = 1.26; CI = 1.09, 1.45) and autonomic nervous system dysfunctions at 7 years. Pregnancy and delivery complications, themselves associated with socioeconomic disadvantage, did not account for the higher risks of neurological abnormalities among disadvantaged children. Parental socioeconomic disadvantage was, independently from pregnancy and delivery complications, associated with abnormal child neural development during the first 7 years of life. These findings reinforce the importance of the early environment for neurodevelopment generally, and expand knowledge regarding the domains of neurodevelopment affected by environmental conditions. Further work is needed to determine the mechanisms linking socioeconomic disadvantage with children's neural functioning, the timing of such mechanisms and their potential reversibility. Published by Oxford University Press on behalf of the International

  15. Dynamical information encoding in neural adaptation.

    PubMed

    Luozheng Li; Wenhao Zhang; Yuanyuan Mi; Dahui Wang; Xiaohan Lin; Si Wu

    2016-08-01

    Adaptation refers to the general phenomenon that a neural system dynamically adjusts its response property according to the statistics of external inputs. In response to a prolonged constant stimulation, neuronal firing rates always first increase dramatically at the onset of the stimulation; and afterwards, they decrease rapidly to a low level close to background activity. This attenuation of neural activity seems to be contradictory to our experience that we can still sense the stimulus after the neural system is adapted. Thus, it prompts a question: where is the stimulus information encoded during the adaptation? Here, we investigate a computational model in which the neural system employs a dynamical encoding strategy during the neural adaptation: at the early stage of the adaptation, the stimulus information is mainly encoded in the strong independent firings; and as time goes on, the information is shifted into the weak but concerted responses of neurons. We find that short-term plasticity, a general feature of synapses, provides a natural mechanism to achieve this goal. Furthermore, we demonstrate that with balanced excitatory and inhibitory inputs, this correlation-based information can be read out efficiently. The implications of this study on our understanding of neural information encoding are discussed.

  16. Responses of single cells in cat visual cortex to prolonged stimulus movement: neural correlates of visual aftereffects.

    PubMed

    Vautin, R G; Berkley, M A

    1977-09-01

    1. The activity of single cortical cells in area 17 of anesthetized and unanesthetized cats was recorded in response to prolonged stimulation with moving stimuli. 2. Under the appropriate conditions, all cells observed showed a progressive response decrement during the stimulation period, regardless of cell classification, i.e., simple, complex, or hypercomplex. 3. The observed response decrement was shown to be largely cortical in origin and could be adequately described with an exponential function of the form R = Rf +(R1-Rf)e-t/T. Time constants derived from such calculations yielded values ranging from 1.92 to 12.45 s under conditions of optimal-stimulation. 4. Most cells showed poststimulation effects, usually a brief period of reduced responsiveness that recovered exponentially. Recovery was essentially complete in about 5-35 s. 5. The degree to which stimuli were effective at inducing response was shown to have significant effects on the magnitude of the response decrement. 6. Several cells showed neural patterns of response and recovery that suggested the operation of intracortical inhibitory mechanisms. 7. A simple two-process model that adequately describes the behavior of all the studied cells is presented. 8. Because the properties of the cells studied correlate well with human psychophysical measures of contour and movement adaptation and recovery, a causal relationship to similar neural mechanisms in humans is suggested.

  17. Sex differences of gray matter morphology in cortico-limbic-striatal neural system in major depressive disorder.

    PubMed

    Kong, Lingtao; Chen, Kaiyuan; Womer, Fay; Jiang, Wenyan; Luo, Xingguang; Driesen, Naomi; Liu, Jie; Blumberg, Hilary; Tang, Yanqing; Xu, Ke; Wang, Fei

    2013-06-01

    Sex differences are observed in both epidemiological and clinical aspects of major depressive disorder (MDD). The cortico-limbic-striatal neural system, including the prefrontal cortex, amygdala, hippocampus, and striatum, have shown sexually dimorphic morphological features and have been implicated in the dysfunctional regulation of mood and emotion in MDD. In this study, we utilized a whole-brain, voxel-based approach to examine sex differences in the regional distribution of gray matter (GM) morphological abnormalities in medication-naïve participants with MDD. Participants included 29 medication-naïve individuals with MDD (16 females and 13 males) and 33 healthy controls (HC) (17 females and 16 males). Gray matter morphology of the cortico-limbic-striatal neural system was examined using voxel-based morphometry analyzes of high-resolution structural magnetic resonance imaging scans. The main effect of diagnosis and interaction effect of diagnosis by sex on GM morphology were statistically significant (p < 0.05, corrected) in the left ventral prefrontal cortex, right amygdala, right hippocampus and bilateral caudate when comparing the MDD and HC groups. Posthoc analyzes showed that females with MDD had significant GM decreases in limbic regions (p < 0.05, corrected), compared to female HC; while males with MDD demonstrated significant GM reduction in striatal regions, (p < 0.05, corrected), compared to HC males. The observed sex-related patterns of abnormalities within the cortico-limbic-strial neural system, such as predominant prefrontal-limbic abnormalities in MDD females vs. predominant prefrontal-striatal abnormalities in MDD males, suggest differences in neural circuitry that may mediate sex differences in the clinical presentation of MDD and potential targets for sex-differentiated treatment of the disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. An abnormal Ca2+ response in mutant sarcomere protein–mediated familial hypertrophic cardiomyopathy

    PubMed Central

    Fatkin, Diane; McConnell, Bradley K.; Mudd, James O.; Semsarian, Christopher; Moskowitz, Ivan G.P.; Schoen, Frederick J.; Giewat, Michael; Seidman, Christine E.; Seidman, J.G.

    2000-01-01

    Dominant-negative sarcomere protein gene mutations cause familial hypertrophic cardiomyopathy (FHC), a disease characterized by left-ventricular hypertrophy, angina, and dyspnea that can result in sudden death. We report here that a murine model of FHC bearing a cardiac myosin heavy-chain gene missense mutation (αMHC403/+), when treated with calcineurin inhibitors or a K+-channel agonist, developed accentuated hypertrophy, worsened histopathology, and was at risk for early death. Despite distinct pharmacologic targets, each agent augmented diastolic Ca2+ concentrations in wild-type cardiac myocytes; αMHC403/+ myocytes failed to respond. Pretreatment with a Ca2+-channel antagonist abrogated diastolic Ca2+ changes in wild-type myocytes and prevented the exaggerated hypertrophic response of treated αMHC403/+ mice. We conclude that FHC-causing sarcomere protein gene mutations cause abnormal Ca2+ responses that initiate a hypertrophic response. These data define an important Ca2+-dependent step in the pathway by which mutant sarcomere proteins trigger myocyte growth and remodel the heart, provide definitive evidence that environment influences progression of FHC, and suggest a rational therapeutic approach to this prevalent human disease. PMID:11104788

  19. Synchronization Control of Neural Networks With State-Dependent Coefficient Matrices.

    PubMed

    Zhang, Junfeng; Zhao, Xudong; Huang, Jun

    2016-11-01

    This brief is concerned with synchronization control of a class of neural networks with state-dependent coefficient matrices. Being different from the existing drive-response neural networks in the literature, a novel model of drive-response neural networks is established. The concepts of uniformly ultimately bounded (UUB) synchronization and convex hull Lyapunov function are introduced. Then, by using the convex hull Lyapunov function approach, the UUB synchronization design of the drive-response neural networks is proposed, and a delay-independent control law guaranteeing the bounded synchronization of the neural networks is constructed. All present conditions are formulated in terms of bilinear matrix inequalities. By comparison, it is shown that the neural networks obtained in this brief are less conservative than those ones in the literature, and the bounded synchronization is suitable for the novel drive-response neural networks. Finally, an illustrative example is given to verify the validity of the obtained results.

  20. Emotion regulation in social anxiety disorder: behavioral and neural responses to three socio-emotional tasks

    PubMed Central

    2013-01-01

    Background Social anxiety disorder (SAD) is thought to involve deficits in emotion regulation, and more specifically, deficits in cognitive reappraisal. However, evidence for such deficits is mixed. Methods Using functional magnetic resonance imaging (fMRI) of blood oxygen-level dependent (BOLD) signal, we examined reappraisal-related behavioral and neural responses in 27 participants with generalized SAD and 27 healthy controls (HC) during three socio-emotional tasks: (1) looming harsh faces (Faces); (2) videotaped actors delivering social criticism (Criticism); and (3) written autobiographical negative self-beliefs (Beliefs). Results Behaviorally, compared to HC, participants with SAD had lesser reappraisal-related reduction in negative emotion in the Beliefs task. Neurally, compared to HC, participants with SAD had lesser BOLD responses in reappraisal-related brain regions when reappraising faces, in visual and attention related regions when reappraising criticism, and in the left superior temporal gyrus when reappraising beliefs. Examination of the temporal dynamics of BOLD responses revealed late reappraisal-related increased responses in HC, compared to SAD. In addition, the dorsomedial prefrontal cortex (DMPFC), which showed reappraisal-related increased activity in both groups, had similar temporal dynamics in SAD and HC during the Faces and Criticism tasks, but greater late response increases in HC, compared to SAD, during the Beliefs task. Reappraisal-related greater late DMPFC responses were associated with greater percent reduction in negative emotion ratings in SAD patients. Conclusions These results suggest a dysfunction of cognitive reappraisal in SAD patients, with overall reduced late brain responses in prefrontal regions, particularly when reappraising faces. Decreased late activity in the DMPFC might be associated with deficient reappraisal and greater negative reactivity. Trial registration ClinicalTrials.gov identifier: NCT00380731 PMID

  1. Abnormal auditory forward masking pattern in the brainstem response of individuals with Asperger syndrome

    PubMed Central

    Källstrand, Johan; Olsson, Olle; Nehlstedt, Sara Fristedt; Sköld, Mia Ling; Nielzén, Sören

    2010-01-01

    Abnormal auditory information processing has been reported in individuals with autism spectrum disorders (ASD). In the present study auditory processing was investigated by recording auditory brainstem responses (ABRs) elicited by forward masking in adults diagnosed with Asperger syndrome (AS). Sixteen AS subjects were included in the forward masking experiment and compared to three control groups consisting of healthy individuals (n = 16), schizophrenic patients (n = 16) and attention deficit hyperactivity disorder patients (n = 16), respectively, of matching age and gender. The results showed that the AS subjects exhibited abnormally low activity in the early part of their ABRs that distinctly separated them from the three control groups. Specifically, wave III amplitudes were significantly lower in the AS group than for all the control groups in the forward masking condition (P < 0.005), which was not the case in the baseline condition. Thus, electrophysiological measurements of ABRs to complex sound stimuli (eg, forward masking) may lead to a better understanding of the underlying neurophysiology of AS. Future studies may further point to specific ABR characteristics in AS individuals that separate them from individuals diagnosed with other neurodevelopmental diseases. PMID:20628629

  2. Diabetes and apoptosis: neural crest cells and neural tube.

    PubMed

    Chappell, James H; Wang, Xiao Dan; Loeken, Mary R

    2009-12-01

    Birth defects resulting from diabetic pregnancy are associated with apoptosis of a critical mass of progenitor cells early during the formation of the affected organ(s). Insufficient expression of genes that regulate viability of the progenitor cells is responsible for the apoptosis. In particular, maternal diabetes inhibits expression of a gene, Pax3, that encodes a transcription factor which is expressed in neural crest and neuroepithelial cells. As a result of insufficient Pax3, cardiac neural crest and neuroepithelial cells undergo apoptosis by a process dependent on the p53 tumor suppressor protein. This, then provides a cellular explanation for the cardiac outflow tract and neural tube and defects induced by diabetic pregnancy.

  3. Diabetes and apoptosis: neural crest cells and neural tube

    PubMed Central

    Chappell, James H.; Dan Wang, Xiao

    2016-01-01

    Birth defects resulting from diabetic pregnancy are associated with apoptosis of a critical mass of progenitor cells early during the formation of the affected organ(s). Insufficient expression of genes that regulate viability of the progenitor cells is responsible for the apoptosis. In particular, maternal diabetes inhibits expression of a gene, Pax3, that encodes a transcription factor which is expressed in neural crest and neuroepithelial cells. As a result of insufficient Pax3, cardiac neural crest and neuroepithelial cells undergo apoptosis by a process dependent on the p53 tumor suppressor protein. This, then provides a cellular explanation for the cardiac outflow tract and neural tube and defects induced by diabetic pregnancy. PMID:19333760

  4. Aging affects neural precision of speech encoding

    PubMed Central

    Anderson, Samira; Parbery-Clark, Alexandra; White-Schwoch, Travis; Kraus, Nina

    2012-01-01

    Older adults frequently report they can hear what is said but cannot understand the meaning, especially in noise. This difficulty may arise from the inability to process rapidly changing elements of speech. Aging is accompanied by a general slowing of neural processing and decreased neural inhibition, both of which likely interfere with temporal processing in auditory and other sensory domains. Age-related reductions in inhibitory neurotransmitter levels and delayed neural recovery can contribute to decreases in the auditory system’s temporal precision. Decreased precision may lead to neural timing delays, reductions in neural response magnitude, and a disadvantage in processing the rapid acoustic changes in speech. The auditory brainstem response (ABR), a scalp-recorded electrical potential, is known for its ability to capture precise neural synchrony within subcortical auditory nuclei; therefore, we hypothesized that a loss of temporal precision results in subcortical timing delays and decreases in response consistency and magnitude. To assess this hypothesis, we recorded ABRs to the speech syllable /da/ in normal hearing younger (ages 18 to 30) and older adult humans (60 to 67). Older adults had delayed ABRs, especially in response to the rapidly changing formant transition, and greater response variability. We also found that older adults had decreased phase locking and smaller response magnitudes than younger adults. Taken together, our results support the theory that older adults have a loss of temporal precision in subcortical encoding of sound, which may account, at least in part, for their difficulties with speech perception. PMID:23055485

  5. FMRI Study of Neural Responses to Implicit Infant Emotion in Anorexia Nervosa

    PubMed Central

    Leppanen, Jenni; Cardi, Valentina; Paloyelis, Yannis; Simmons, Andy; Tchanturia, Kate; Treasure, Janet

    2017-01-01

    Difficulties in social–emotional processing have been proposed to play an important role in the development and maintenance of anorexia nervosa (AN). Few studies, thus far, have investigated neural processes that underlie these difficulties, including processing emotional facial expressions. However, the majority of these studies have investigated neural responses to adult emotional display, which may be confounded by elevated sensitivity to social rank and threat in AN. Therefore, the aim of this study was to investigate the neural processes underlying implicit processing of positively and negatively valenced infant emotional display in AN. Twenty-one adult women with AN and twenty-six healthy comparison (HC) women were presented with images of positively valenced, negatively valenced, and neutral infant faces during a fMRI scan. Significant differences between the groups in positive > neutral and negative > neutral contrasts were investigated in a priori regions of interest, including the bilateral amygdala, insula, and lateral prefrontal cortex (PFC). The findings revealed that the AN participants showed relatively increased recruitment while the HC participants showed relatively reduced recruitment of the bilateral amygdala and the right dorsolateral PFC in the positive > neutral contrast. In the negative > neutral contrast, the AN group showed relatively increased recruitment of the left posterior insula while the HC groups showed relatively reduced recruitment of this region. These findings suggest that people with AN may engage in implicit prefrontal down-regulation of elevated limbic reactivity to positively social–emotional stimuli. PMID:28567026

  6. Blunted Neural Response to Rewards as a Prospective Predictor of the Development of Depression in Adolescent Girls.

    PubMed

    Nelson, Brady D; Perlman, Greg; Klein, Daniel N; Kotov, Roman; Hajcak, Greg

    2016-12-01

    A blunted neural response to rewards has recently emerged as a potential mechanistic biomarker of adolescent depression. The reward positivity, an event-related potential elicited by feedback indicating monetary gain relative to loss, has been associated with risk for depression. The authors examined whether the reward positivity prospectively predicted the development of depression 18 months later in a large community sample of adolescent girls. The sample included 444 girls 13.5-15.5 years old with no lifetime history of a depressive disorder, along with a biological parent for each girl. At baseline, the adolescents' reward positivity was measured using a monetary guessing task, their current depressive symptoms were assessed using a self-report questionnaire, and the adolescents' and parents' lifetime psychiatric histories were evaluated with diagnostic interviews. The same interview and questionnaire were administered to the adolescents again approximately 18 months later. A blunted reward positivity at baseline predicted first-onset depressive disorder and greater depressive symptom scores 18 months later. The reward positivity was also a significant predictor independent of other prominent risk factors, including baseline depressive symptoms and adolescent and parental lifetime psychiatric history. The combination of a blunted reward positivity and greater depressive symptom scores at baseline provided the greatest positive predictive value for first-onset depressive disorder. This study provides strong converging evidence that a blunted neural response to rewards precedes adolescent-onset depression and symptom emergence. Blunted neural response may therefore constitute an important target for screening and prevention.

  7. The trait of sensory processing sensitivity and neural responses to changes in visual scenes

    PubMed Central

    Xu, Xiaomeng; Aron, Arthur; Aron, Elaine; Cao, Guikang; Feng, Tingyong; Weng, Xuchu

    2011-01-01

    This exploratory study examined the extent to which individual differences in sensory processing sensitivity (SPS), a temperament/personality trait characterized by social, emotional and physical sensitivity, are associated with neural response in visual areas in response to subtle changes in visual scenes. Sixteen participants completed the Highly Sensitive Person questionnaire, a standard measure of SPS. Subsequently, they were tested on a change detection task while undergoing functional magnetic resonance imaging (fMRI). SPS was associated with significantly greater activation in brain areas involved in high-order visual processing (i.e. right claustrum, left occipitotemporal, bilateral temporal and medial and posterior parietal regions) as well as in the right cerebellum, when detecting minor (vs major) changes in stimuli. These findings remained strong and significant after controlling for neuroticism and introversion, traits that are often correlated with SPS. These results provide the first evidence of neural differences associated with SPS, the first direct support for the sensory aspect of this trait that has been studied primarily for its social and affective implications, and preliminary evidence for heightened sensory processing in individuals high in SPS. PMID:20203139

  8. Assessment of the developmental totipotency of neural cells in the cerebral cortex of mouse embryo by nuclear transfer

    PubMed Central

    Yamazaki, Yukiko; Makino, Hatsune; Hamaguchi-Hamada, Kayoko; Hamada, Shun; Sugino, Hidehiko; Kawase, Eihachiro; Miyata, Takaki; Ogawa, Masaharu; Yanagimachi, Ryuzo; Yagi, Takeshi

    2001-01-01

    When neural cells were collected from the entire cerebral cortex of developing mouse fetuses (15.5–17.5 days postcoitum) and their nuclei were transferred into enucleated oocytes, 5.5% of the reconstructed oocytes developed into normal offspring. This success rate was the highest among all previous mouse cloning experiments that used somatic cells. Forty-four percent of live embryos at 10.5 days postcoitum were morphologically normal when premature and early-postmitotic neural cells from the ventricular side of the cortex were used. In contrast, the majority (95%) of embryos were morphologically abnormal (including structural abnormalities in the neural tube) when postmitotic-differentiated neurons from the pial side of the cortex were used for cloning. Whereas 4.3% of embryos cloned with ventricular-side cells developed into healthy offspring, only 0.5% of those cloned with differentiated neurons in the pial side did so. These facts seem to suggest that the nuclei of neural cells in advanced stages of differentiation had lost their developmental totipotency. The underlying mechanism for this developmental limitation could be somatic DNA rearrangements in differentiating neural cells. PMID:11698647

  9. Are lexical tones musical? Native language's influence on neural response to pitch in different domains.

    PubMed

    Chen, Ao; Peter, Varghese; Wijnen, Frank; Schnack, Hugo; Burnham, Denis

    2018-04-21

    Language experience shapes musical and speech pitch processing. We investigated whether speaking a lexical tone language natively modulates neural processing of pitch in language and music as well as their correlation. We tested tone language (Mandarin Chinese), and non-tone language (Dutch) listeners in a passive oddball paradigm measuring mismatch negativity (MMN) for (i) Chinese lexical tones and (ii) three-note musical melodies with similar pitch contours. For lexical tones, Chinese listeners showed a later MMN peak than the non-tone language listeners, whereas for MMN amplitude there were no significant differences between groups. Dutch participants also showed a late discriminative negativity (LDN). In the music condition two MMNs, corresponding to the two notes that differed between the standard and the deviant were found for both groups, and an LDN were found for both the Dutch and the Chinese listeners. The music MMNs were significantly right lateralized. Importantly, significant correlations were found between the lexical tone and the music MMNs for the Dutch but not the Chinese participants. The results suggest that speaking a tone language natively does not necessarily enhance neural responses to pitch either in language or in music, but that it does change the nature of neural pitch processing: non-tone language speakers appear to perceive lexical tones as musical, whereas for tone language speakers, lexical tones and music may activate different neural networks. Neural resources seem to be assigned differently for the lexical tones and for musical melodies, presumably depending on the presence or absence of long-term phonological memory traces. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Relationship between Parental Feeding Practices and Neural Responses to Food Cues in Adolescents

    PubMed Central

    Chambers, Alison; Blissett, Jacqueline; Chechlacz, Magdalena; Barrett, Timothy; Higgs, Suzanne; Nouwen, Arie

    2016-01-01

    parental teaching and modelling of behaviour. Parental restrictive feeding and parental teaching and modelling affected neural responses to food cues in different ways, depending on motivations and diagnoses, illustrating a social influence on neural responses to food cues. PMID:27479051

  11. Relationship between Parental Feeding Practices and Neural Responses to Food Cues in Adolescents.

    PubMed

    Allen, Harriet A; Chambers, Alison; Blissett, Jacqueline; Chechlacz, Magdalena; Barrett, Timothy; Higgs, Suzanne; Nouwen, Arie

    2016-01-01

    parental teaching and modelling of behaviour. Parental restrictive feeding and parental teaching and modelling affected neural responses to food cues in different ways, depending on motivations and diagnoses, illustrating a social influence on neural responses to food cues.

  12. Response inhibition in psychopathy: the frontal N2 and P3.

    PubMed

    Munro, Gillian E S; Dywan, Jane; Harris, Grant T; McKee, Shari; Unsal, Ayse; Segalowitz, Sidney J

    2007-05-17

    Psychopathy has been associated with atypical function of the anterior cingulate cortex (ACC) and adjacent brain regions and with abnormalities in performance monitoring, which is thought to rely on these structures. The ACC and adjacent regions are also involved in the generation of two characteristic components of the event-related potential: the frontal N2 and P3. Both components are enhanced when a response is withheld (NoGo trial) within a series of positive-responses (Go trials) and are considered an index of response inhibition. We recorded event-related potentials while violent offenders who varied on the dimension of psychopathy and non-offender controls performed a Go/NoGo task. The offenders made more errors of commission on NoGo trials but this effect was unrelated to level of psychopathy within the group and, inconsistent with a previous report, they produced the enhanced frontal N2 and P3 effect in response to NoGo relative to Go conditions. We conclude that the neural processes involved in response inhibition are not abnormal in psychopaths when both stimuli and context are affectively neutral and suggest that a more nuanced perspective regarding impulsivity in this population be considered.

  13. Low-level neural auditory discrimination dysfunctions in specific language impairment-A review on mismatch negativity findings.

    PubMed

    Kujala, Teija; Leminen, Miika

    2017-12-01

    In specific language impairment (SLI), there is a delay in the child's oral language skills when compared with nonverbal cognitive abilities. The problems typically relate to phonological and morphological processing and word learning. This article reviews studies which have used mismatch negativity (MMN) in investigating low-level neural auditory dysfunctions in this disorder. With MMN, it is possible to tap the accuracy of neural sound discrimination and sensory memory functions. These studies have found smaller response amplitudes and longer latencies for speech and non-speech sound changes in children with SLI than in typically developing children, suggesting impaired and slow auditory discrimination in SLI. Furthermore, they suggest shortened sensory memory duration and vulnerability of the sensory memory to masking effects. Importantly, some studies reported associations between MMN parameters and language test measures. In addition, it was found that language intervention can influence the abnormal MMN in children with SLI, enhancing its amplitude. These results suggest that the MMN can shed light on the neural basis of various auditory and memory impairments in SLI, which are likely to influence speech perception. Copyright © 2017. Published by Elsevier Ltd.

  14. Neural correlates of response inhibition in current and former smokers.

    PubMed

    Weywadt, Christina R; Kiehl, Kent A; Claus, Eric D

    2017-02-15

    Loss of behavioral control is a hallmark of addiction. Individual differences in basic cognitive processes such as response inhibition may be important for interrupting automatic behaviors associated with smoking and supporting prolonged abstinence. To examine how response inhibition and error monitoring processes differ as a function of smoking status, current smokers, former smokers and never smokers (N=126) completed a simple Go/No-Go task while undergoing functional magnetic resonance imaging. All groups performed similarly on the task and similarly engaged the inferior frontal gyrus and dorsal anterior cingulate cortex, regions traditionally associated with response inhibition and error monitoring, respectively. During response inhibition (i.e., Correct Rejects>Hits contrast), overall group differences emerged in the recruitment of the cerebellum, while individual group differences in error monitoring (False Alarms>Hits contrast) were seen for regions of the parietal lobe and thalamus (current smokers>former smokers), as well as regions of the bilateral cerebellum, parahippocampal gyrus and superior parietal lobe (i.e., ever smokers>never smokers). We discuss how our results replicate two previous large-sample studies that used the same Go/No-Go task and review these data in terms of network models of inhibitory and error monitoring abnormalities in addiction. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Behavioral and neural responses to infant and adult tears: The impact of maternal love withdrawal.

    PubMed

    Riem, Madelon M E; van IJzendoorn, Marinus H; De Carli, Pietro; Vingerhoets, Ad J J M; Bakermans-Kranenburg, Marian J

    2017-09-01

    The current study examined behavioral and neural responses to infant and adult tears, taking into account childhood experiences with parental love-withdrawal. With functional MRI (fMRI), we measured neural reactivity to pictures of infants and adults with and without tears on their faces in nulliparous women with varying childhood experiences of maternal use of love withdrawal. Behavioral responses to infant and adult tears were measured with an approach-avoidance task. We found that individuals with experiences of love withdrawal showed less amygdala and insula reactivity to adult tears, but love withdrawal did not affect amygdala and insula reactivity to infant tears. During the approach-avoidance task, individuals responded faster to adult tears in the approach condition compared with the avoidance condition, indicating that adult tears facilitate approach behavior. Individuals responded faster to infant tears than to adult tears, regardless of approach or avoidance condition. Our findings suggest that infant tears are highly salient and may, therefore, overrule the effects of contextual and personal characteristics that influence the perception of adult crying. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  16. Impulsive traits and unplanned suicide attempts predict exaggerated prefrontal response to angry faces in the elderly

    PubMed Central

    Vanyukov, Polina M.; Szanto, Katalin; Siegle, Greg J.; Hallquist, Michael N.; Reynolds, Charles F.; Aizenstein, Howard J.; Dombrovski, Alexandre Y.

    2015-01-01

    Objectives Abnormal responses to social stimuli are seen in people vulnerable to suicidal behavior, indicating possible disruptions in the neural circuitry mediating the interpretation of socio-emotional cues. These disruptions have not been empirically related to psychological and cognitive pathways to suicide. In the present study of older suicide attempters, we examined neural responses to emotional faces and their relationship to impulsivity, one of the components of the suicidal diathesis. Methods Using functional magnetic resonance imaging, we recorded neuro-hemodynamic responses to angry faces in a carefully-characterized sample of 18 depressed elderly with history of suicide attempts, 13 depressed non-suicidal patients, and 18 healthy individuals, all aged 60+. Impulsivity was assessed with the Social Problem Solving Inventory Impulsivity/Carelessness Style subscale and Barratt Impulsiveness Scale. The Suicide Intent Scale planning subscale was used to describe the degree of planning associated with the most lethal attempt. Results Depression and history of attempted suicide were not associated with neural responses to angry faces, failing to replicate earlier studies. Higher impulsivity, however, predicted exaggerated responses to angry faces in fronto-opercular and dorsomedial prefrontal cortex (pcorr < .05). Poorly planned suicide attempts also predicted increased fronto-opercular responses. Results were robust to effects of medication exposure, comorbid anxiety and addiction, severity of depression, burden of physical illness, and possible brain injury from suicide attempts. Conclusions Impulsive traits and history of unplanned suicide attempts partly explain the heterogeneity in neural responses to angry faces in depressed elderly. Displays of social emotion command excessive cortical processing in impulsive suicide attempters. PMID:25529800

  17. Altered neural responses to heat pain in drug-naive patients with Parkinson disease.

    PubMed

    Forkmann, Katarina; Grashorn, Wiebke; Schmidt, Katharina; Fründt, Odette; Buhmann, Carsten; Bingel, Ulrike

    2017-08-01

    Pain is a frequent but still neglected nonmotor symptom of Parkinson disease (PD). However, neural mechanisms underlying pain in PD are poorly understood. Here, we explored whether the high prevalence of pain in PD might be related to dysfunctional descending pain control. Using functional magnetic resonance imaging we explored neural responses during the anticipation and processing of heat pain in 21 PD patients (Hoehn and Yahr I-III) and 23 healthy controls (HC). Parkinson disease patients were naive to dopaminergic medication to avoid confounding drug effects. Fifteen heat pain stimuli were applied to the participants' forearm. Intensity and unpleasantness ratings were provided for each stimulus. Subjective pain perception was comparable for PD patients and HC. Neural processing, however, differed between groups: PD patients showed lower activity in several descending pain modulation regions (dorsal anterior cingulate cortex [dACC], subgenual anterior cingulate cortex, and dorsolateral prefrontal cortex [DLPFC]) and lower functional connectivity between dACC and DLPFC during pain anticipation. Parkinson disease symptom severity was negatively correlated with dACC-DLPFC connectivity indicating impaired functional coupling of pain modulatory regions with disease progression. During pain perception PD patients showed higher midcingulate cortex activity compared with HC, which also scaled with PD severity. Interestingly, dACC-DLPFC connectivity during pain anticipation was negatively associated with midcingulate cortex activity during the receipt of pain in PD patients. This study indicates altered neural processing during the anticipation and receipt of experimental pain in drug-naive PD patients. It provides first evidence for a progressive decline in descending pain modulation in PD, which might be related to the high prevalence of pain in later stages of PD.

  18. Serotonin 2A Receptor Signaling Underlies LSD-induced Alteration of the Neural Response to Dynamic Changes in Music.

    PubMed

    Barrett, Frederick S; Preller, Katrin H; Herdener, Marcus; Janata, Petr; Vollenweider, Franz X

    2017-09-28

    Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Active Control of Wind-Tunnel Model Aeroelastic Response Using Neural Networks

    NASA Technical Reports Server (NTRS)

    Scott, Robert C.

    2000-01-01

    NASA Langley Research Center, Hampton, VA 23681 Under a joint research and development effort conducted by the National Aeronautics and Space Administration and The Boeing Company (formerly McDonnell Douglas) three neural-network based control systems were developed and tested. The control systems were experimentally evaluated using a transonic wind-tunnel model in the Langley Transonic Dynamics Tunnel. One system used a neural network to schedule flutter suppression control laws, another employed a neural network in a predictive control scheme, and the third employed a neural network in an inverse model control scheme. All three of these control schemes successfully suppressed flutter to or near the limits of the testing apparatus, and represent the first experimental applications of neural networks to flutter suppression. This paper will summarize the findings of this project.

  20. Neural Correlates of Inhibition and Contextual Cue Processing Related to Treatment Response in PTSD

    PubMed Central

    van Rooij, Sanne JH; Geuze, Elbert; Kennis, Mitzy; Rademaker, Arthur R; Vink, Matthijs

    2015-01-01

    Thirty to fifty percent of posttraumatic stress disorder (PTSD) patients do not respond to treatment. Understanding the neural mechanisms underlying treatment response could contribute to improve response rates. PTSD is often associated with decreased inhibition of fear responses in a safe environment. Importantly, the mechanism of effective treatment (psychotherapy) relies on inhibition and so-called contextual cue processing. Therefore, we investigate inhibition and contextual cue processing in the context of treatment. Forty-one male war veterans with PTSD and 22 healthy male war veterans (combat controls) were scanned twice with a 6- to 8-month interval, in which PTSD patients received treatment (psychotherapy). We distinguished treatment responders from nonresponders on the base of percentage symptom decrease. Inhibition and contextual cue processing were assessed with the stop-signal anticipation task. Behavioral and functional MRI measures were compared between PTSD patients and combat controls, and between responders and nonresponders using repeated measures analyses. PTSD patients showed behavioral and neural deficits in inhibition and contextual cue processing at both time points compared with combat controls. These deficits were unaffected by treatment; therefore, they likely represent vulnerability factors or scar aspects of PTSD. Second, responders showed increased pretreatment activation of the left inferior parietal lobe (IPL) during contextual cue processing compared with nonresponders. Moreover, left IPL activation predicted percentage symptom improvement. The IPL has an important role in contextual cue processing, and may therefore facilitate the effect of psychotherapy. Hence, increased left IPL activation may represent a potential predictive biomarker for PTSD treatment response. PMID:25154707

  1. Distinct Neural-Functional Effects of Treatments With Selective Serotonin Reuptake Inhibitors, Electroconvulsive Therapy, and Transcranial Magnetic Stimulation and Their Relations to Regional Brain Function in Major Depression: A Meta-analysis.

    PubMed

    Chau, David T; Fogelman, Phoebe; Nordanskog, Pia; Drevets, Wayne C; Hamilton, J Paul

    2017-05-01

    Functional neuroimaging studies have examined the neural substrates of treatments for major depressive disorder (MDD). Low sample size and methodological heterogeneity, however, undermine the generalizability of findings from individual studies. We conducted a meta-analysis to identify reliable neural changes resulting from different modes of treatment for MDD and compared them with each other and with reliable neural functional abnormalities observed in depressed versus control samples. We conducted a meta-analysis of studies reporting changes in brain activity (e.g., as indexed by positron emission tomography) following treatments with selective serotonin reuptake inhibitors (SSRIs), electroconvulsive therapy (ECT), or transcranial magnetic stimulation. Additionally, we examined the statistical reliability of overlap among thresholded meta-analytic SSRI, ECT, and transcranial magnetic stimulation maps as well as a map of abnormal neural function in MDD. Our meta-analysis revealed that 1) SSRIs decrease activity in the anterior insula, 2) ECT decreases activity in central nodes of the default mode network, 3) transcranial magnetic stimulation does not result in reliable neural changes, and 4) regional effects of these modes of treatment do not significantly overlap with each other or with regions showing reliable functional abnormality in MDD. SSRIs and ECT produce neurally distinct effects relative to each other and to the functional abnormalities implicated in depression. These treatments therefore may exert antidepressant effects by diminishing neural functions not implicated in depression but that nonetheless impact mood. We discuss how the distinct neural changes resulting from SSRIs and ECT can account for both treatment effects and side effects from these therapies as well as how to individualize these treatments. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Noninvasive beat-to-beat finger arterial pressure monitoring during orthostasis: a comprehensive review of normal and abnormal responses at different ages.

    PubMed

    van Wijnen, V K; Finucane, C; Harms, M P M; Nolan, H; Freeman, R L; Westerhof, B E; Kenny, R A; Ter Maaten, J C; Wieling, W

    2017-12-01

    Over the past 30 years, noninvasive beat-to-beat blood pressure (BP) monitoring has provided great insight into cardiovascular autonomic regulation during standing. Although traditional sphygmomanometric measurement of BP may be sufficient for detection of sustained orthostatic hypotension, it fails to capture the complexity of the underlying dynamic BP and heart rate responses. With the emerging use of noninvasive beat-to-beat BP monitoring for the assessment of orthostatic BP control in clinical and population studies, various definitions for abnormal orthostatic BP patterns have been used. Here, age-related changes in cardiovascular control in healthy subjects will be reviewed to define the spectrum of the most important abnormal orthostatic BP patterns within the first 180 s of standing. Abnormal orthostatic BP responses can be defined as initial orthostatic hypotension (a transient systolic BP fall of >40 mmHg within 15 s of standing), delayed BP recovery (an inability of systolic BP to recover to a value of >20 mmHg below baseline at 30 s after standing) and sustained orthostatic hypotension (a sustained decline in systolic BP of ≥20 mmHg occurring 60-180 s after standing). In the evaluation of patients with light-headedness, pre(syncope), (unexplained) falls or suspected autonomic dysfunction, it is essential to distinguish between normal cardiovascular autonomic regulation and these abnormal orthostatic BP responses. The prevalence, clinical relevance and underlying pathophysiological mechanisms of these patterns differ significantly across the lifespan. Initial orthostatic hypotension is important for identifying causes of syncope in younger adults, whereas delayed BP recovery and sustained orthostatic hypotension are essential for evaluating the risk of falls in older adults. © 2017 The Authors Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

  3. Acute LSD effects on response inhibition neural networks.

    PubMed

    Schmidt, A; Müller, F; Lenz, C; Dolder, P C; Schmid, Y; Zanchi, D; Lang, U E; Liechti, M E; Borgwardt, S

    2017-10-02

    Recent evidence shows that the serotonin 2A receptor (5-hydroxytryptamine2A receptor, 5-HT2AR) is critically involved in the formation of visual hallucinations and cognitive impairments in lysergic acid diethylamide (LSD)-induced states and neuropsychiatric diseases. However, the interaction between 5-HT2AR activation, cognitive impairments and visual hallucinations is still poorly understood. This study explored the effect of 5-HT2AR activation on response inhibition neural networks in healthy subjects by using LSD and further tested whether brain activation during response inhibition under LSD exposure was related to LSD-induced visual hallucinations. In a double-blind, randomized, placebo-controlled, cross-over study, LSD (100 µg) and placebo were administered to 18 healthy subjects. Response inhibition was assessed using a functional magnetic resonance imaging Go/No-Go task. LSD-induced visual hallucinations were measured using the 5 Dimensions of Altered States of Consciousness (5D-ASC) questionnaire. Relative to placebo, LSD administration impaired inhibitory performance and reduced brain activation in the right middle temporal gyrus, superior/middle/inferior frontal gyrus and anterior cingulate cortex and in the left superior frontal and postcentral gyrus and cerebellum. Parahippocampal activation during response inhibition was differently related to inhibitory performance after placebo and LSD administration. Finally, activation in the left superior frontal gyrus under LSD exposure was negatively related to LSD-induced cognitive impairments and visual imagery. Our findings show that 5-HT2AR activation by LSD leads to a hippocampal-prefrontal cortex-mediated breakdown of inhibitory processing, which might subsequently promote the formation of LSD-induced visual imageries. These findings help to better understand the neuropsychopharmacological mechanisms of visual hallucinations in LSD-induced states and neuropsychiatric disorders.

  4. Neural correlates of the behavioral-autonomic interaction response to potentially threatening stimuli

    PubMed Central

    Farrow, Tom F. D.; Johnson, Naomi K.; Hunter, Michael D.; Barker, Anthony T.; Wilkinson, Iain D.; Woodruff, Peter W. R.

    2013-01-01

    Subjective assessment of emotional valence is typically associated with both brain activity and autonomic arousal. Accurately assessing emotional salience is particularly important when perceiving threat. We sought to characterize the neural correlates of the interaction between behavioral and autonomic responses to potentially threatening visual and auditory stimuli. Twenty-five healthy male subjects underwent fMRI scanning whilst skin conductance responses (SCR) were recorded. One hundred and eighty pictures, sentences, and sounds were assessed as “harmless” or “threatening.” Individuals' stimulus-locked, phasic SCRs and trial-by-trial behavioral assessments were entered as regressors into a flexible factorial design to establish their separate autonomic and behavioral neural correlates, and convolved to examine psycho-autonomic interaction (PAI) effects. Across all stimuli, “threatening,” compared with “harmless” behavioral assessments were associated with mainly frontal and precuneus activation with specific within-modality activations including bilateral parahippocampal gyri (pictures), bilateral anterior cingulate cortex (ACC) and frontal pole (sentences), and right Heschl's gyrus and bilateral temporal gyri (sounds). Across stimulus modalities SCRs were associated with activation of parieto-occipito-thalamic regions, an activation pattern which was largely replicated within-modality. In contrast, PAI analyses revealed modality-specific activations including right fusiform/parahippocampal gyrus (pictures), right insula (sentences), and mid-cingulate gyrus (sounds). Phasic SCR activity was positively correlated with an individual's propensity to assess stimuli as “threatening.” SCRs may modulate cognitive assessments on a “harmless–threatening” dimension, thereby modulating affective tone and hence behavior. PMID:23335893

  5. Streptozotocin induced oxidative stress, innate immune system responses and behavioral abnormalities in male mice.

    PubMed

    Amiri, Shayan; Haj-Mirzaian, Arya; Momeny, Majid; Amini-Khoei, Hossein; Rahimi-Balaei, Maryam; Poursaman, Simin; Rastegar, Mojgan; Nikoui, Vahid; Mokhtari, Tahmineh; Ghazi-Khansari, Mahmoud; Hosseini, Mir-Jamal

    2017-01-06

    Recent evidence indicates the involvement of inflammatory factors and mitochondrial dysfunction in the etiology of psychiatric disorders such as anxiety and depression. To investigate the possible role of mitochondrial-induced sterile inflammation in the co-occurrence of anxiety and depression, in this study, we treated adult male mice with the intracerebroventricular (i.c.v.) infusion of a single low dose of streptozotocin (STZ, 0.2mg/mouse). Using valid and qualified behavioral tests for the assessment of depressive and anxiety-like behaviors, we showed that STZ-treated mice exhibited behaviors relevant to anxiety and depression 24h following STZ treatment. We observed that the co-occurrence of anxiety and depressive-like behaviors in animals were associated with abnormal mitochondrial function, nitric oxide overproduction and, the increased activity of cytosolic phospholipase A 2 (cPLA 2 ) in the hippocampus. Further, STZ-treated mice had a significant upregulation of genes associated with the innate immune system such as toll-like receptors 2 and 4. Pathological evaluations showed no sign of neurodegeneration in the hippocampus of STZ-treated mice. Results of this study revealed that behavioral abnormalities provoked by STZ, as a cytotoxic agent that targets mitochondria and energy metabolism, are associated with abnormal mitochondrial activity and, consequently the initiation of innate-inflammatory responses in the hippocampus. Our findings highlight the role of mitochondria and innate immunity in the formation of sterile inflammation and behaviors relevant to anxiety and depression. Also, we have shown that STZ injection (i.c.v.) might be an animal model for depression and anxiety disorders based on sterile inflammation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Connecting Teratogen-Induced Congenital Heart Defects to Neural Crest Cells and Their Effect on Cardiac Function

    PubMed Central

    Karunamuni, Ganga H.; Ma, Pei; Gu, Shi; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

    2014-01-01

    Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest is in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies. PMID:25220155

  7. The neural mechanisms of semantic and response conflicts: an fMRI study of practice-related effects in the Stroop task.

    PubMed

    Chen, Zhencai; Lei, Xu; Ding, Cody; Li, Hong; Chen, Antao

    2013-02-01

    Previous studies have demonstrated that there are separate neural mechanisms underlying semantic and response conflicts in the Stroop task. However, the practice effects of these conflicts need to be elucidated and the possible involvements of common neural mechanisms are yet to be established. We employed functional magnetic resonance imaging (fMRI) in a 4-2 mapping practice-related Stroop task to determine the neural substrates under these conflicts. Results showed that different patterns of brain activations are associated with practice in the attentional networks (e.g., dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and posterior parietal cortex (PPC)) for both conflicts, response control regions (e.g., inferior frontal junction (IFJ), inferior frontal gyrus (IFG)/insula, and pre-supplementary motor areas (pre-SMA)) for semantic conflict, and posterior cortex for response conflict. We also found areas of common activation in the left hemisphere within the attentional networks, for the early practice stage in semantic conflict and the late stage in "pure" response conflict using conjunction analysis. The different practice effects indicate that there are distinct mechanisms underlying these two conflict types: semantic conflict practice effects are attributable to the automation of stimulus processing, conflict and response control; response conflict practice effects are attributable to the proportional increase of conflict-related cognitive resources. In addition, the areas of common activation suggest that the semantic conflict effect may contain a partial response conflict effect, particularly at the beginning of the task. These findings indicate that there are two kinds of response conflicts contained in the key-pressing Stroop task: the vocal-level (mainly in the early stage) and key-pressing (mainly in the late stage) response conflicts; thus, the use of the subtraction method for the exploration of semantic and response conflicts

  8. Dissociable neural mechanisms underlying response-based and familiarity-based conflict in working memory.

    PubMed

    Nelson, James K; Reuter-Lorenz, Patricia A; Sylvester, Ching-Yune C; Jonides, John; Smith, Edward E

    2003-09-16

    Cognitive control requires the resolution of interference among competing and potentially conflicting representations. Such conflict can emerge at different points between stimulus input and response generation, with the net effect being that of compromising performance. The goal of this article was to dissociate the neural mechanisms underlying different sources of conflict to elucidate the architecture of the neural systems that implement cognitive control. By using functional magnetic resonance imaging and a verbal working memory task (item recognition), we examined brain activity related to two kinds of conflict with comparable behavioral consequences. In a trial of our item-recognition task, participants saw four letters, followed by a retention interval, and a probe letter that did or did not match one of the letters held in working memory (positive probe and negative probe, respectively). On some trials, conflict arose solely because of the current negative probe having a high familiarity, due to its membership in the immediately preceding trial's target set. On other trials, additional conflict arose because of the current negative probe having also been a positive probe on the immediately preceding trial, producing response-level conflict. Consistent with previous work, conflict due to high familiarity was associated with left prefrontal activation, but not with anterior cingulate activation. The response-conflict condition, when compared with high-familiarity conflict trials, was associated with anterior cingulate cortex activation, but with no additional left prefrontal activation. This double dissociation points to differing contributions of specific cortical areas to cognitive control, which are based on the source of conflict.

  9. Condition monitoring of 3G cellular networks through competitive neural models.

    PubMed

    Barreto, Guilherme A; Mota, João C M; Souza, Luis G M; Frota, Rewbenio A; Aguayo, Leonardo

    2005-09-01

    We develop an unsupervised approach to condition monitoring of cellular networks using competitive neural algorithms. Training is carried out with state vectors representing the normal functioning of a simulated CDMA2000 network. Once training is completed, global and local normality profiles (NPs) are built from the distribution of quantization errors of the training state vectors and their components, respectively. The global NP is used to evaluate the overall condition of the cellular system. If abnormal behavior is detected, local NPs are used in a component-wise fashion to find abnormal state variables. Anomaly detection tests are performed via percentile-based confidence intervals computed over the global and local NPs. We compared the performance of four competitive algorithms [winner-take-all (WTA), frequency-sensitive competitive learning (FSCL), self-organizing map (SOM), and neural-gas algorithm (NGA)] and the results suggest that the joint use of global and local NPs is more efficient and more robust than current single-threshold methods.

  10. Neural mechanism of the pressor response to obstructive and nonobstructive apnea.

    PubMed

    Katragadda, S; Xie, A; Puleo, D; Skatrud, J B; Morgan, B J

    1997-12-01

    Obstructive and nonobstructive apneas elicit substantial increases in muscle sympathetic nerve activity and arterial pressure. The time course of change in these variables suggests a causal relationship; however, mechanical influences, such as release of negative intrathoracic pressure and reinflation of the lungs, are potential contributors to the arterial pressure rise. To test the hypothesis that apnea-induced pressor responses are neurally mediated, we measured arterial pressure (photoelectric plethysmography), muscle sympathetic nerve activity (peroneal microneurography), arterial O2 saturation (pulse oximeter), and end-tidal CO2 tension (gas analyzer) during sustained Mueller maneuvers, intermittent Mueller maneuvers, and simple breath holds in six healthy humans before, during, and after ganglionic blockade with trimethaphan (3-4 mg/min, titrated to produce complete disappearance of sympathetic bursts from the neurogram). Ganglionic blockade abolished the pressor responses to sustained and intermittent Mueller maneuvers (-4 +/- 1 vs. +15 +/- 3 and 0 +/- 2 vs. +15 +/- 5 mmHg) and breath holds (0 +/- 3 vs. +11 +/- 3, all P < 0.05). We conclude that the acute pressor response to obstructive and nonobstructive voluntary apnea is sympathetically mediated.

  11. Neural-fuzzy control system application for monitoring process response and control of anaerobic hybrid reactor in wastewater treatment and biogas production.

    PubMed

    Waewsak, Chaiwat; Nopharatana, Annop; Chaiprasert, Pawinee

    2010-01-01

    Based on the developed neural-fuzzy control system for anaerobic hybrid reactor (AHR) in wastewater treatment and biogas production, the neural network with backpropagation algorithm for prediction of the variables pH, alkalinity (Alk) and total volatile acids (TVA) at present day time t was used as input data for the fuzzy logic to calculate the influent feed flow rate that was applied to control and monitor the process response at different operations in the initial, overload influent feeding and the recovery phases. In all three phases, this neural-fuzzy control system showed great potential to control AHR in high stability and performance and quick response. Although in the overloading operation phase II with two fold calculating influent flow rate together with a two fold organic loading rate (OLR), this control system had rapid response and was sensitive to the intended overload. When the influent feeding rate was followed by the calculation of control system in the initial operation phase I and the recovery operation phase III, it was found that the neural-fuzzy control system application was capable of controlling the AHR in a good manner with the pH close to 7, TVA/Alk < 0.4 and COD removal > 80% with biogas and methane yields at 0.45 and 0.30 m3/kg COD removed.

  12. Us versus Them: Social Identity Shapes Neural Responses to Intergroup Competition and Harm

    PubMed Central

    Cikara, Mina; Botvinick, Matthew M.; Fiske, Susan T.

    2013-01-01

    Intergroup competition makes social identity salient, which affects how people respond to competitors’ hardships. The failures of a fellow group member are painful, while those of a rival group member may give pleasure—a feeling that may motivate harming rivals. The present study examines whether valuation-related neural responses to rival groups’ failures correlate with likelihood of harming individuals associated with those rivals. Avid fans of the Red Sox and Yankees teams viewed baseball plays while undergoing fMRI. Subjectively negative outcomes (favored-failure, rival-success) activated anterior cingulate cortex and insula, while positive outcomes (favored-success, rival-failure—even against a third team) activated ventral striatum. The ventral striatum effect, associated with subjective pleasure, also correlated with self-reported likelihood of aggressing against a fan of the rival team (controlling for general aggression). Outcomes of social group competition can directly affect primary reward-processing neural systems, with implications for intergroup harm. PMID:21270447

  13. Neural Responses to Visual Food Cues According to Weight Status: A Systematic Review of Functional Magnetic Resonance Imaging Studies

    PubMed Central

    Pursey, Kirrilly M.; Stanwell, Peter; Callister, Robert J.; Brain, Katherine; Collins, Clare E.; Burrows, Tracy L.

    2014-01-01

    Emerging evidence from recent neuroimaging studies suggests that specific food-related behaviors contribute to the development of obesity. The aim of this review was to report the neural responses to visual food cues, as assessed by functional magnetic resonance imaging (fMRI), in humans of differing weight status. Published studies to 2014 were retrieved and included if they used visual food cues, studied humans >18 years old, reported weight status, and included fMRI outcomes. Sixty studies were identified that investigated the neural responses of healthy weight participants (n = 26), healthy weight compared to obese participants (n = 17), and weight-loss interventions (n = 12). High-calorie food images were used in the majority of studies (n = 36), however, image selection justification was only provided in 19 studies. Obese individuals had increased activation of reward-related brain areas including the insula and orbitofrontal cortex in response to visual food cues compared to healthy weight individuals, and this was particularly evident in response to energy dense cues. Additionally, obese individuals were more responsive to food images when satiated. Meta-analysis of changes in neural activation post-weight loss revealed small areas of convergence across studies in brain areas related to emotion, memory, and learning, including the cingulate gyrus, lentiform nucleus, and precuneus. Differential activation patterns to visual food cues were observed between obese, healthy weight, and weight-loss populations. Future studies require standardization of nutrition variables and fMRI outcomes to enable more direct comparisons between studies. PMID:25988110

  14. Neural responses to visual food cues according to weight status: a systematic review of functional magnetic resonance imaging studies.

    PubMed

    Pursey, Kirrilly M; Stanwell, Peter; Callister, Robert J; Brain, Katherine; Collins, Clare E; Burrows, Tracy L

    2014-01-01

    Emerging evidence from recent neuroimaging studies suggests that specific food-related behaviors contribute to the development of obesity. The aim of this review was to report the neural responses to visual food cues, as assessed by functional magnetic resonance imaging (fMRI), in humans of differing weight status. Published studies to 2014 were retrieved and included if they used visual food cues, studied humans >18 years old, reported weight status, and included fMRI outcomes. Sixty studies were identified that investigated the neural responses of healthy weight participants (n = 26), healthy weight compared to obese participants (n = 17), and weight-loss interventions (n = 12). High-calorie food images were used in the majority of studies (n = 36), however, image selection justification was only provided in 19 studies. Obese individuals had increased activation of reward-related brain areas including the insula and orbitofrontal cortex in response to visual food cues compared to healthy weight individuals, and this was particularly evident in response to energy dense cues. Additionally, obese individuals were more responsive to food images when satiated. Meta-analysis of changes in neural activation post-weight loss revealed small areas of convergence across studies in brain areas related to emotion, memory, and learning, including the cingulate gyrus, lentiform nucleus, and precuneus. Differential activation patterns to visual food cues were observed between obese, healthy weight, and weight-loss populations. Future studies require standardization of nutrition variables and fMRI outcomes to enable more direct comparisons between studies.

  15. Altered Immune Function Associated with Disordered Neural Connectivity and Executive Dysfunctions: A Neurophysiological Study on Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Han, Yvonne M. Y.; Chan, Agnes S.; Sze, Sophia L.; Cheung, Mei-Chun; Wong, Chun-kwok; Lam, Joseph M. K.; Poon, Priscilla M. K.

    2013-01-01

    Previous studies have shown that children with autism spectrum disorders (ASDs) have impaired executive function, disordered neural connectivity, and abnormal immunologic function. The present study examined whether these abnormalities were associated. Seventeen high-functioning (HFA) and 17 low-functioning (LFA) children with ASD, aged 8-17…

  16. Aberrant Hyperconnectivity in the Motor System at Rest Is Linked to Motor Abnormalities in Schizophrenia Spectrum Disorders.

    PubMed

    Walther, Sebastian; Stegmayer, Katharina; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Viher, Petra V

    2017-09-01

    Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity. Principal component analyses of motor behavioral data produced 4 factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). Motor factors were correlated with connectivity values. Schizophrenia was characterized by hyperconnectivity in 3 main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity. Therefore, altered functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. Unsupervised Pattern Classifier for Abnormality-Scaling of Vibration Features for Helicopter Gearbox Fault Diagnosis

    NASA Technical Reports Server (NTRS)

    Jammu, Vinay B.; Danai, Kourosh; Lewicki, David G.

    1996-01-01

    A new unsupervised pattern classifier is introduced for on-line detection of abnormality in features of vibration that are used for fault diagnosis of helicopter gearboxes. This classifier compares vibration features with their respective normal values and assigns them a value in (0, 1) to reflect their degree of abnormality. Therefore, the salient feature of this classifier is that it does not require feature values associated with faulty cases to identify abnormality. In order to cope with noise and changes in the operating conditions, an adaptation algorithm is incorporated that continually updates the normal values of the features. The proposed classifier is tested using experimental vibration features obtained from an OH-58A main rotor gearbox. The overall performance of this classifier is then evaluated by integrating the abnormality-scaled features for detection of faults. The fault detection results indicate that the performance of this classifier is comparable to the leading unsupervised neural networks: Kohonen's Feature Mapping and Adaptive Resonance Theory (AR72). This is significant considering that the independence of this classifier from fault-related features makes it uniquely suited to abnormality-scaling of vibration features for fault diagnosis.

  18. Coronary vasomotor abnormalities in insulin-resistant individuals.

    PubMed

    Quiñones, Manuel J; Hernandez-Pampaloni, Miguel; Schelbert, Heinrich; Bulnes-Enriquez, Isabel; Jimenez, Xochitl; Hernandez, Gustavo; De La Rosa, Roxana; Chon, Yun; Yang, Huiying; Nicholas, Susanne B; Modilevsky, Tamara; Yu, Katherine; Van Herle, Katja; Castellani, Lawrence W; Elashoff, Robert; Hsueh, Willa A

    2004-05-04

    Insulin resistance is a metabolic spectrum that progresses from hyperinsulinemia to the metabolic syndrome, impaired glucose tolerance, and finally type 2 diabetes mellitus. It is unclear when vascular abnormalities begin in this spectrum of metabolic effects. To evaluate the association of insulin resistance with the presence and reversibility of coronary vasomotor abnormalities in young adults at low cardiovascular risk. Cross-sectional study followed by prospective, open-label treatment study. University hospital. 50 insulin-resistant and 22 insulin-sensitive, age-matched Mexican-American participants without glucose intolerance or traditional risk factors for or evidence of coronary artery disease. 3 months of thiazolidinedione therapy for 25 insulin-resistant patients. Glucose infusion rate in response to insulin infusion was used to define insulin resistance (glucose infusion rate < or = 4.00 mg/kg of body weight per minute [range, 0.90 to 3.96 mg/kg per minute]) and insulin sensitivity (glucose infusion rate > or = 7.50 mg/kg per minute [range, 7.52 to 13.92 mg/kg per minute]). Myocardial blood flow was measured by using positron emission tomography at rest, during cold pressor test (largely endothelium-dependent), and after dipyridamole administration (largely vascular smooth muscle-dependent). Myocardial blood flow responses to dipyridamole were similar in the insulin-sensitive and insulin-resistant groups. However, myocardial blood flow response to cold pressor test increased by 47.6% from resting values in insulin-sensitive patients and by 14.4% in insulin-resistant patients. During thiazolidinedione therapy in a subgroup of insulin-resistant patients, insulin sensitivity improved, fasting plasma insulin levels decreased, and myocardial blood flow responses to cold pressor test normalized. The study was not randomized, and it included only 1 ethnic group. Insulin-resistant patients who do not have hypercholesterolemia or hypertension and do not smoke

  19. Histological evaluation of flexible neural implants; flexibility limit for reducing the tissue response?

    NASA Astrophysics Data System (ADS)

    Lee, Heui Chang; Ejserholm, Fredrik; Gaire, Janak; Currlin, Seth; Schouenborg, Jens; Wallman, Lars; Bengtsson, Martin; Park, Kinam; Otto, Kevin J.

    2017-06-01

    Objective. Flexible neural probes are hypothesized to reduce the chronic foreign body response (FBR) mainly by reducing the strain-stress caused by an interplay between the tethered probe and the brain’s micromotion. However, a large discrepancy of Young’s modulus still exists (3-6 orders of magnitude) between the flexible probes and the brain tissue. This raises the question of whether we need to bridge this gap; would increasing the probe flexibility proportionally reduce the FBR? Approach. Using novel off-stoichiometry thiol-enes-epoxy (OSTE+) polymer probes developed in our previous work, we quantitatively evaluated the FBR to four types of probes with different softness: silicon (~150 GPa), polyimide (1.5 GPa), OSTE+Hard (300 MPa), and OSTE+Soft (6 MPa). Main results. We observed a significant reduction in the fluorescence intensity of biomarkers for activated microglia/macrophages and blood-brain barrier (BBB) leakiness around the three soft polymer probes compared to the silicon probe, both at 4 weeks and 8 weeks post-implantation. However, we did not observe any consistent differences in the biomarkers among the polymer probes. Significance. The results suggest that the mechanical compliance of neural probes can mediate the degree of FBR, but its impact diminishes after a hypothetical threshold level. This infers that resolving the mechanical mismatch alone has a limited effect on improving the lifetime of neural implants.

  20. Association between amygdala response to emotional faces and social anxiety in autism spectrum disorders.

    PubMed

    Kleinhans, Natalia M; Richards, Todd; Weaver, Kurt; Johnson, L Clark; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth

    2010-10-01

    Difficulty interpreting facial expressions has been reported in autism spectrum disorders (ASD) and is thought to be associated with amygdala abnormalities. To further explore the neural basis of abnormal emotional face processing in ASD, we conducted an fMRI study of emotional face matching in high-functioning adults with ASD and age, IQ, and gender matched controls. In addition, we investigated whether there was a relationship between self-reported social anxiety and fMRI activation. During fMRI scanning, study participants were instructed to match facial expressions depicting fear or anger. The control condition was a comparable shape-matching task. The control group evidenced significantly increased left prefrontal activation and decreased activation in the occipital lobes compared to the ASD group during emotional face matching. Further, within the ASD group, greater social anxiety was associated with increased activation in right amygdala and left middle temporal gyrus, and decreased activation in the fusiform face area. These results indicate that level of social anxiety mediates the neural response to emotional face perception in ASD. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Candy and the Brain: Neural Response to Candy Gains and Losses

    PubMed Central

    Luking, Katherine R; Barch, Deanna M

    2013-01-01

    Incentive processing is a critical component of a host of cognitive processes including attention, motivation, and learning. Neuroimaging studies have clarified the neural systems underlying processing of primary and secondary rewards in adults. However, current reward paradigms have hindered comparison across these reward types as well as between age groups. To address methodological issues regarding timing of incentive delivery (during versus post-scan) and the age-appropriateness of the incentive type we utilized fMRI and a modified version of a card guessing game (CGG), where candy pieces delivered post-scan served as the reinforcer, to investigate neural responses to incentives. Healthy young adults aged 22–26 years won and lost large and small amounts of candy based on their ability to guess the number on a mystery card. BOLD activity was compared following candy gain (large/small), loss (large/small) and neutral feedback. During candy gains, adults recruited regions typically involved in response to monetary and other rewards such as the caudate, putamen, and orbitofrontal cortex. During losses, adults displayed greater deactivation in the hippocampus compared to neutral and gain feedback. Additionally, individual difference analyses suggested a negative relationship between reward sensitivity (assessed by behavioral inhibition/behavioral activation scales) and the difference between high and low magnitude losses in the caudate and lateral orbitofrontal cortex. Also within the striatum greater punishment sensitivity was positively related to the difference in activity following high compared to low gains. Overall these results show strong overlap with those from previous monetary versions of the CGG and provide a baseline for future work with developmental populations. PMID:23519971

  2. Novel transformation-based response prediction of shear building using interval neural network

    NASA Astrophysics Data System (ADS)

    Chakraverty, S.; Sahoo, Deepti Moyi

    2017-04-01

    Present paper uses powerful technique of interval neural network (INN) to simulate and estimate structural response of multi-storey shear buildings subject to earthquake motion. The INN is first trained for a real earthquake data, viz., the ground acceleration as input and the numerically generated responses of different floors of multi-storey buildings as output. Till date, no model exists to handle positive and negative data in the INN. As such here, the bipolar data in [ -1, 1] are converted first to unipolar form, i.e., to [0, 1] by means of a novel transformation for the first time to handle the above training patterns in normalized form. Once the training is done, again the unipolar data are converted back to its bipolar form by using the inverse transformation. The trained INN architecture is then used to simulate and test the structural response of different floors for various intensity earthquake data and it is found that the predicted responses given by INN model are good for practical purposes.

  3. Neural assembly computing.

    PubMed

    Ranhel, João

    2012-06-01

    Spiking neurons can realize several computational operations when firing cooperatively. This is a prevalent notion, although the mechanisms are not yet understood. A way by which neural assemblies compute is proposed in this paper. It is shown how neural coalitions represent things (and world states), memorize them, and control their hierarchical relations in order to perform algorithms. It is described how neural groups perform statistic logic functions as they form assemblies. Neural coalitions can reverberate, becoming bistable loops. Such bistable neural assemblies become short- or long-term memories that represent the event that triggers them. In addition, assemblies can branch and dismantle other neural groups generating new events that trigger other coalitions. Hence, such capabilities and the interaction among assemblies allow neural networks to create and control hierarchical cascades of causal activities, giving rise to parallel algorithms. Computing and algorithms are used here as in a nonstandard computation approach. In this sense, neural assembly computing (NAC) can be seen as a new class of spiking neural network machines. NAC can explain the following points: 1) how neuron groups represent things and states; 2) how they retain binary states in memories that do not require any plasticity mechanism; and 3) how branching, disbanding, and interaction among assemblies may result in algorithms and behavioral responses. Simulations were carried out and the results are in agreement with the hypothesis presented. A MATLAB code is available as a supplementary material.

  4. The Neural Circuit Mechanisms Underlying the Retinal Response to Motion Reversal

    PubMed Central

    Chen, Eric Y.; Chou, Janice; Park, Jeongsook; Schwartz, Greg

    2014-01-01

    To make up for delays in visual processing, retinal circuitry effectively predicts that a moving object will continue moving in a straight line, allowing retinal ganglion cells to anticipate the object's position. However, a sudden reversal of motion triggers a synchronous burst of firing from a large group of ganglion cells, possibly signaling a violation of the retina's motion prediction. To investigate the neural circuitry underlying this response, we used a combination of multielectrode array and whole-cell patch recordings to measure the responses of individual retinal ganglion cells in the tiger salamander to reversing stimuli. We found that different populations of ganglion cells were responsible for responding to the reversal of different kinds of objects, such as bright versus dark objects. Using pharmacology and designed stimuli, we concluded that ON and OFF bipolar cells both contributed to the reversal response, but that amacrine cells had, at best, a minor role. This allowed us to formulate an adaptive cascade model (ACM), similar to the one previously used to describe ganglion cell responses to motion onset. By incorporating the ON pathway into the ACM, we were able to reproduce the time-varying firing rate of fast OFF ganglion cells for all experimentally tested stimuli. Analysis of the ACM demonstrates that bipolar cell gain control is primarily responsible for generating the synchronized retinal response, as individual bipolar cells require a constant time delay before recovering from gain control. PMID:25411485

  5. Knockdown of zebrafish Fancd2 causes developmental abnormalities via p53-dependent apoptosis.

    PubMed

    Liu, Ting Xi; Howlett, Niall G; Deng, Min; Langenau, David M; Hsu, Karl; Rhodes, Jennifer; Kanki, John P; D'Andrea, Alan D; Look, A Thomas

    2003-12-01

    Mechanisms underlying the multiple developmental defects observed in Fanconi anemia (FA) patients are not well defined. We have identified the zebrafish homolog of human FANCD2, which encodes a nuclear effector protein that is monoubiquitinated in response to DNA damage, targeting it to nuclear foci where it preserves chromosomal integrity. Fancd2-deficient zebrafish embryos develop defects similar to those found in children with FA, including shortened body length, microcephaly, and microophthalmia, which are due to extensive cellular apoptosis. Developmental defects and increased apoptosis in Fancd2-deficient zebrafish were corrected by injection of human FANCD2 or zebrafish bcl2 mRNA, or by knockdown of p53, indicating that in the absence of Fancd2, developing tissues spontaneously undergo p53-dependent apoptosis. Thus, Fancd2 is essential during embryogenesis to prevent inappropriate apoptosis in neural cells and other tissues undergoing high levels of proliferative expansion, implicating this mechanism in the congenital abnormalities observed in human infants with FA.

  6. Neural response to catecholamine depletion in remitted bulimia nervosa: Relation to depression and relapse.

    PubMed

    Mueller, Stefanie Verena; Mihov, Yoan; Federspiel, Andrea; Wiest, Roland; Hasler, Gregor

    2017-07-01

    Bulimia nervosa has been associated with a dysregulated catecholamine system. Nevertheless, the influence of this dysregulation on bulimic symptoms, on neural activity, and on the course of the illness is not clear yet. An instructive paradigm for directly investigating the relationship between catecholaminergic functioning and bulimia nervosa has involved the behavioral and neural responses to experimental catecholamine depletion. The purpose of this study was to examine the neural substrate of catecholaminergic dysfunction in bulimia nervosa and its relationship to relapse. In a randomized, double-blind and crossover study design, catecholamine depletion was achieved by using the oral administration of alpha-methyl-paratyrosine (AMPT) over 24 h in 18 remitted bulimic (rBN) and 22 healthy (HC) female participants. Cerebral blood flow (CBF) was measured using a pseudo continuous arterial spin labeling (pCASL) sequence. In a follow-up telephone interview, bulimic relapse was assessed. Following AMPT, rBN participants revealed an increased vigor reduction and CBF decreases in the pallidum and posterior midcingulate cortex (pMCC) relative to HC participants showing no CBF changes in these regions. These results indicated that the pallidum and the pMCC are the functional neural correlates of the dysregulated catecholamine system in bulimia nervosa. Bulimic relapse was associated with increased depressive symptoms and CBF reduction in the hippocampus/parahippocampal gyrus following catecholamine depletion. AMPT-induced increased CBF in this region predicted staying in remission. These findings demonstrated the importance of depressive symptoms and the stress system in the course of bulimia nervosa. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. What they bring: baseline psychological distress differentially predicts neural response in social exclusion by children's friends and strangers in best friend dyads.

    PubMed

    Baddam, Suman; Laws, Holly; Crawford, Jessica L; Wu, Jia; Bolling, Danielle Z; Mayes, Linda C; Crowley, Michael J

    2016-11-01

    Friendships play a major role in cognitive, emotional and social development in middle childhood. We employed the online Cyberball social exclusion paradigm to understand the neural correlates of dyadic social exclusion among best friends assessed simultaneously. Each child played with their friend and an unfamiliar player. Event-related potentials (ERPs) were assessed via electroencephalogram during exclusion by friend and unfamiliar peer. Data were analyzed with hierarchical linear modeling to account for nesting of children within friendship dyads. Results showed that stranger rejection was associated with larger P2 and positive slow wave ERP responses compared to exclusion by a friend. Psychological distress differentially moderated the effects of friend and stranger exclusion such that children with greater psychological distress were observed to have larger neural responses (larger P2 and slow wave) to exclusion by a stranger compared to exclusion by a friend. Conversely, children with lower levels of psychological distress had larger neural responses for exclusion by a friend than by a stranger. Psychological distress within the dyad differentially predicted the P2 and slow wave response. Findings highlight the prominent, but differential role of individual and dyadic psychological distress levels in moderating responses to social exclusion in middle childhood. © The Author (2016). Published by Oxford University Press.

  8. Blunted neural response to anticipation, effort and consummation of reward and aversion in adolescents with depression symptomatology.

    PubMed

    Rzepa, Ewelina; Fisk, Jennifer; McCabe, Ciara

    2017-03-01

    Neural reward function has been proposed as a possible biomarker for depression. However, how the neural response to reward and aversion might differ in young adolescents with current symptoms of depression is as yet unclear. Thirty-three adolescents were recruited, 17 scoring low on the Mood and Feelings Questionnaire (low risk group) and 16 scoring high (high risk group). Our functional magnetic resonance imaging task measured; anticipation (pleasant/unpleasant cue), effort (achieve a pleasant taste or avoid an unpleasant taste) and consummation (pleasant/unpleasant tastes) in regions of interest; ventral medial prefrontal cortex, pregenual cingulate cortex, the insula and ventral striatum. We also examined whole brain group differences. In the regions of interest analysis we found reduced activity in the high risk group in the pregenual cingulate cortex during anticipation and reduced pregenual cingulate cortex and ventral medial prefrontal cortex during effort and consummation. In the whole brain analysis we also found reduced activity in the high risk group in the prefrontal cortex and the precuneus during anticipation. We found reduced activity in the hippocampus during the effort phase and in the anterior cingulate/frontal pole during consummation in the high risk group. Increased anhedonia measures correlated with decreased pregenual cingulate cortex activity during consummation in the high risk group only. Our results are the first to show that adolescents with depression symptoms have blunted neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This study suggests that interventions in young people at risk of depression, that can reverse blunted responses, might be beneficial as preventative strategies.

  9. Social cognition in members of conflict groups: behavioural and neural responses in Arabs, Israelis and South Americans to each other's misfortunes

    PubMed Central

    Bruneau, Emile G.; Dufour, Nicholas; Saxe, Rebecca

    2012-01-01

    In contexts of cultural conflict, people delegitimize the other group's perspective and lose compassion for the other group's suffering. These psychological biases have been empirically characterized in intergroup settings, but rarely in groups involved in active conflict. Similarly, the basic brain networks involved in recognizing others' narratives and misfortunes have been identified, but how these brain networks are modulated by intergroup conflict is largely untested. In the present study, we examined behavioural and neural responses in Arab, Israeli and South American participants while they considered the pain and suffering of individuals from each group. Arabs and Israelis reported feeling significantly less compassion for each other's pain and suffering (the ‘conflict outgroup’), but did not show an ingroup bias relative to South Americans (the ‘distant outgroup’). In contrast, the brain regions that respond to others' tragedies showed an ingroup bias relative to the distant outgroup but not the conflict outgroup, particularly for descriptions of emotional suffering. Over all, neural responses to conflict group members were qualitatively different from neural responses to distant group members. This is the first neuroimaging study to examine brain responses to others' suffering across both distant and conflict groups, and provides a first step towards building a foundation for the biological basis of conflict. PMID:22271787

  10. Social cognition in members of conflict groups: behavioural and neural responses in Arabs, Israelis and South Americans to each other's misfortunes.

    PubMed

    Bruneau, Emile G; Dufour, Nicholas; Saxe, Rebecca

    2012-03-05

    In contexts of cultural conflict, people delegitimize the other group's perspective and lose compassion for the other group's suffering. These psychological biases have been empirically characterized in intergroup settings, but rarely in groups involved in active conflict. Similarly, the basic brain networks involved in recognizing others' narratives and misfortunes have been identified, but how these brain networks are modulated by intergroup conflict is largely untested. In the present study, we examined behavioural and neural responses in Arab, Israeli and South American participants while they considered the pain and suffering of individuals from each group. Arabs and Israelis reported feeling significantly less compassion for each other's pain and suffering (the 'conflict outgroup'), but did not show an ingroup bias relative to South Americans (the 'distant outgroup'). In contrast, the brain regions that respond to others' tragedies showed an ingroup bias relative to the distant outgroup but not the conflict outgroup, particularly for descriptions of emotional suffering. Over all, neural responses to conflict group members were qualitatively different from neural responses to distant group members. This is the first neuroimaging study to examine brain responses to others' suffering across both distant and conflict groups, and provides a first step towards building a foundation for the biological basis of conflict.

  11. Neural Coding Mechanisms in Gustation.

    DTIC Science & Technology

    1980-09-15

    world is composed of four primary tastes ( sweet , sour, salty , and bitter), and that each of these is carried by a separate and private neural line, thus...ted sweet -sour- salty -bitter types. The mathematical method of analysis was hierarchical cluster analysis based on the responses of many neurons (20 to...block number) Taste Neural coding Neural organization Stimulus organization Olfaction AB TRACT M~ea -i .rvm~ .1* N necffas and idmatity by block mmnbwc

  12. Abnormal myocardial repolarisation in response to hypoxaemia and fenoterol.

    PubMed Central

    Kiely, D. G.; Cargill, R. I.; Grove, A.; Struthers, A. D.; Lipworth, B. J.

    1995-01-01

    BACKGROUND--Prolongation of the QTc interval has been associated with cardiac dysrhythmias and sudden death. QTc dispersion (interlead variability in QTc interval) has recently been proposed as being a more sensitive marker of repolarisation abnormalities and shown to be a more specific index of arrhythmia risk. Although hypoxaemia and fenoterol have previously been shown to prolong the QTc interval, this does not reflect regional myocardial repolarisation abnormalities. METHODS--Electrophysiological effects were measured at baseline and after 30 minutes steady state hypoxaemia at an arterial oxygen saturation (SaO2) of 75-80% (study 1) and at baseline then 30 minutes after inhaled fenoterol 2.4 mg (study 2). From the ECG, lead II corrected QT interval (QTc) and overall corrected QT dispersion were measured using a computer linked digitising tablet according to standard criteria. RESULTS--QTc dispersion was increased during hypoxia compared with baseline values (mean (SE) 69 (6) ms v 50 (5) ms) and after fenoterol compared with baseline (79 (13) v 46 (4) ms), respectively. There was also an increase in QTc interval and heart rate after fenoterol (493 (23) v 420 (6) ms and 98 (3) v 71 (6) bpm, respectively). The heart rate was increased during hypoxaemia compared with baseline (78 (3) v 64 (2) bpm), but no change occurred in the QTc interval. CONCLUSIONS--Both hypoxaemia and fenoterol cause myocardial repolarisation abnormalities in man in terms of increased QTc dispersion, but only fenoterol increased the QTc interval. This may be relevant in the aetiology of arrhythmias in patients with acute severe asthma where beta agonist therapy and hypoxaemia coexist. PMID:7491554

  13. Subjective and neural responses to intravenous alcohol in young adults with light and heavy drinking patterns.

    PubMed

    Gilman, Jodi M; Ramchandani, Vijay A; Crouss, Tess; Hommer, Daniel W

    2012-01-01

    Heavy alcohol consumption during young adulthood is a risk factor for the development of serious alcohol use disorders. Research has shown that individual differences in subjective responses to alcohol may affect individuals' vulnerability to developing alcoholism. Studies comparing the subjective and objective response to alcohol between light and heavy drinkers (HDs), however, have yielded inconsistent results, and neural responses to alcohol in these groups have not been characterized. We performed a double-blind, placebo-controlled, randomized crossover alcohol challenge study comparing functional magnetic resonance imaging and subjective response to intravenously administered 6% v/v ethanol to a target blood alcohol concentration of 0.08% or placebo between HDs and social drinkers (SDs). During the imaging, we presented emotional cues in order to measure how emotion modulated the effects of alcohol on the brain's reward circuitry. We found that, at equivalent blood alcohol concentrations, HDs reported lower subjective alcohol effects than SDs. Alcohol significantly activated the nucleus accumbens in SDs, but not in HDs. Self-reported ratings of intoxication correlated with striatal activation, suggesting that activation may reflect subjective experience of intoxication. Fearful faces significantly activated the amygdala in the SDs only, and this activation was attenuated by alcohol. This study shows that HDs not only experience reduced subjective effects of alcohol, but also demonstrate a blunted response to alcohol in the brain's reward system. Our findings indicate that reduced subjective and neural response to alcohol in HDs may be suggestive of either the development of tolerance to alcohol, or of pre-existing decreased sensitivity to alcohol's effects.

  14. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence.

    PubMed

    Guyer, Amanda E; Jarcho, Johanna M; Pérez-Edgar, Koraly; Degnan, Kathryn A; Pine, Daniel S; Fox, Nathan A; Nelson, Eric E

    2015-07-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children's caregiving context. The convergence of a child's temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (M(age) = 17.89 years, N = 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development.

  15. Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence

    PubMed Central

    Guyer, Amanda E.; Jarcho, Johanna M.; Pérez-Edgar, Koraly; Degnan, Kathryn A.; Pine, Daniel S.; Fox, Nathan A.; Nelson, Eric E.

    2015-01-01

    Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children’s caregiving context. The convergence of a child’s temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (Mage = 17.89 years, N= 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development. PMID:25588884

  16. Regulation of endogenous neural stem/progenitor cells for neural repair—factors that promote neurogenesis and gliogenesis in the normal and damaged brain

    PubMed Central

    Christie, Kimberly J.; Turnley, Ann M.

    2012-01-01

    Neural stem/precursor cells in the adult brain reside in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. These cells primarily generate neuroblasts that normally migrate to the olfactory bulb (OB) and the dentate granule cell layer respectively. Following brain damage, such as traumatic brain injury, ischemic stroke or in degenerative disease models, neural precursor cells from the SVZ in particular, can migrate from their normal route along the rostral migratory stream (RMS) to the site of neural damage. This neural precursor cell response to neural damage is mediated by release of endogenous factors, including cytokines and chemokines produced by the inflammatory response at the injury site, and by the production of growth and neurotrophic factors. Endogenous hippocampal neurogenesis is frequently also directly or indirectly affected by neural damage. Administration of a variety of factors that regulate different aspects of neural stem/precursor biology often leads to improved functional motor and/or behavioral outcomes. Such factors can target neural stem/precursor proliferation, survival, migration and differentiation into appropriate neuronal or glial lineages. Newborn cells also need to subsequently survive and functionally integrate into extant neural circuitry, which may be the major bottleneck to the current therapeutic potential of neural stem/precursor cells. This review will cover the effects of a range of intrinsic and extrinsic factors that regulate neural stem/precursor cell functions. In particular it focuses on factors that may be harnessed to enhance the endogenous neural stem/precursor cell response to neural damage, highlighting those that have already shown evidence of preclinical effectiveness and discussing others that warrant further preclinical investigation. PMID:23346046

  17. Prefrontal cortex activity during response selection predicts processing speed impairment in schizophrenia

    PubMed Central

    Woodward, Neil D.; Duffy-Alberto, Brittney; Karbasforoushan, Haleh

    2014-01-01

    Processing speed is the most impaired neuropsychological domain in schizophrenia and a robust predictor of functional outcome. Determining the specific cognitive operations underlying processing speed dysfunction and indentifying their neural correlates may assist in developing pro-cognitive interventions. Response selection, the process of mapping stimuli onto motor responses, correlates with neuropsychological tests of processing speed and may contribute to processing speed impairment in schizophrenia. This study investigated the relationship between behavioral and neural measures of response selection, and a neuropsychological index of processing speed in schizophrenia. 26 patients with schizophrenia and 21 healthy subjects underwent fMRI scanning during performance of 2 and 4-choice-reaction time (RT) tasks and completed the Wechsler Adult Intelligence Scale-III (WAIS) Processing Speed Index (PSI). Response selection, defined as RT slowing between 2 and 4-choice RT, was impaired in schizophrenia and correlated with psychometric processing speed. Greater activation of the dorsolateral prefrontal cortex (PFC) was observed in schizophrenia and correlated with poorer WAIS PSI scores. Deficient response selection and abnormal recruitment of the dorsolateral PFC during response selection contribute to processing speed impairment in schizophrenia. Interventions that improve response selection and normalize dorsolateral PFC function may improve processing speed in schizophrenia. PMID:23816240

  18. Early Parenting Moderates the Association between Parental Depression and Neural Reactivity to Rewards and Losses in Offspring.

    PubMed

    Kujawa, Autumn; Proudfit, Greg H; Laptook, Rebecca; Klein, Daniel N

    2015-07-01

    Children of parents with depression exhibit neural abnormalities in reward processing. Examining contributions of parenting could provide insight into the development of these abnormalities and to the etiology of depression. We evaluated whether early parenting moderates the effects of parental depression on a neural measure of reward and loss processing in mid-late childhood. Parenting was assessed when children were preschoolers. At age nine, children completed an event-related potential assessment and the feedback negativity (FN) was measured following rewards and losses ( N =344). Maternal authoritative parenting moderated the effect of maternal depression; among offspring of mothers with histories of depression, low authoritative parenting predicted a blunted FN. Observed maternal positive parenting interacted with paternal depression in a comparable manner, indicating that maternal parenting may buffer the effects of paternal depression. Early parenting may be important in shaping the neural systems involved in reward processing among children at high risk for depression.

  19. Early Parenting Moderates the Association between Parental Depression and Neural Reactivity to Rewards and Losses in Offspring

    PubMed Central

    Kujawa, Autumn; Proudfit, Greg H.; Laptook, Rebecca; Klein, Daniel N.

    2014-01-01

    Children of parents with depression exhibit neural abnormalities in reward processing. Examining contributions of parenting could provide insight into the development of these abnormalities and to the etiology of depression. We evaluated whether early parenting moderates the effects of parental depression on a neural measure of reward and loss processing in mid-late childhood. Parenting was assessed when children were preschoolers. At age nine, children completed an event-related potential assessment and the feedback negativity (FN) was measured following rewards and losses (N=344). Maternal authoritative parenting moderated the effect of maternal depression; among offspring of mothers with histories of depression, low authoritative parenting predicted a blunted FN. Observed maternal positive parenting interacted with paternal depression in a comparable manner, indicating that maternal parenting may buffer the effects of paternal depression. Early parenting may be important in shaping the neural systems involved in reward processing among children at high risk for depression. PMID:26167423

  20. Abnormal frontoparietal synaptic gain mediating the P300 in patients with psychotic disorder and their unaffected relatives.

    PubMed

    Díez, Álvaro; Ranlund, Siri; Pinotsis, Dimitris; Calafato, Stella; Shaikh, Madiha; Hall, Mei-Hua; Walshe, Muriel; Nevado, Ángel; Friston, Karl J; Adams, Rick A; Bramon, Elvira

    2017-06-01

    The "dysconnection hypothesis" of psychosis suggests that a disruption of functional integration underlies cognitive deficits and clinical symptoms. Impairments in the P300 potential are well documented in psychosis. Intrinsic (self-)connectivity in a frontoparietal cortical hierarchy during a P300 experiment was investigated. Dynamic Causal Modeling was used to estimate how evoked activity results from the dynamics of coupled neural populations and how neural coupling changes with the experimental factors. Twenty-four patients with psychotic disorder, twenty-four unaffected relatives, and twenty-five controls underwent EEG recordings during an auditory oddball paradigm. Sixteen frontoparietal network models (including primary auditory, superior parietal, and superior frontal sources) were analyzed and an optimal model of neural coupling, explaining diagnosis and genetic risk effects, as well as their interactions with task condition were identified. The winning model included changes in connectivity at all three hierarchical levels. Patients showed decreased self-inhibition-that is, increased cortical excitability-in left superior frontal gyrus across task conditions, compared with unaffected participants. Relatives had similar increases in excitability in left superior frontal and right superior parietal sources, and a reversal of the normal synaptic gain changes in response to targets relative to standard tones. It was confirmed that both subjects with psychotic disorder and their relatives show a context-independent loss of synaptic gain control at the highest hierarchy levels. The relatives also showed abnormal gain modulation responses to task-relevant stimuli. These may be caused by NMDA-receptor and/or GABAergic pathologies that change the excitability of superficial pyramidal cells and may be a potential biological marker for psychosis. Hum Brain Mapp 38:3262-3276, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.