From Whole-Brain Data to Functional Circuit Models: The Zebrafish Optomotor Response.

PubMed

Naumann, Eva A; Fitzgerald, James E; Dunn, Timothy W; Rihel, Jason; Sompolinsky, Haim; Engert, Florian

2016-11-03

Detailed descriptions of brain-scale sensorimotor circuits underlying vertebrate behavior remain elusive. Recent advances in zebrafish neuroscience offer new opportunities to dissect such circuits via whole-brain imaging, behavioral analysis, functional perturbations, and network modeling. Here, we harness these tools to generate a brain-scale circuit model of the optomotor response, an orienting behavior evoked by visual motion. We show that such motion is processed by diverse neural response types distributed across multiple brain regions. To transform sensory input into action, these regions sequentially integrate eye- and direction-specific sensory streams, refine representations via interhemispheric inhibition, and demix locomotor instructions to independently drive turning and forward swimming. While experiments revealed many neural response types throughout the brain, modeling identified the dimensions of functional connectivity most critical for the behavior. We thus reveal how distributed neurons collaborate to generate behavior and illustrate a paradigm for distilling functional circuit models from whole-brain data. Copyright © 2016 Elsevier Inc. All rights reserved.

Untangling the Effect of Head Acceleration on Brain Responses to Blast Waves

PubMed Central

Mao, Haojie; Unnikrishnan, Ginu; Rakesh, Vineet; Reifman, Jaques

2015-01-01

Multiple injury-causing mechanisms, such as wave propagation, skull flexure, cavitation, and head acceleration, have been proposed to explain blast-induced traumatic brain injury (bTBI). An accurate, quantitative description of the individual contribution of each of these mechanisms may be necessary to develop preventive strategies against bTBI. However, to date, despite numerous experimental and computational studies of bTBI, this question remains elusive. In this study, using a two-dimensional (2D) rat head model, we quantified the contribution of head acceleration to the biomechanical response of brain tissues when exposed to blast waves in a shock tube. We compared brain pressure at the coup, middle, and contre-coup regions between a 2D rat head model capable of simulating all mechanisms (i.e., the all-effects model) and an acceleration-only model. From our simulations, we determined that head acceleration contributed 36–45% of the maximum brain pressure at the coup region, had a negligible effect on the pressure at the middle region, and was responsible for the low pressure at the contre-coup region. Our findings also demonstrate that the current practice of measuring rat brain pressures close to the center of the brain would record only two-thirds of the maximum pressure observed at the coup region. Therefore, to accurately capture the effects of acceleration in experiments, we recommend placing a pressure sensor near the coup region, especially when investigating the acceleration mechanism using different experimental setups. PMID:26458125

Differences in Regional Brain Responses to Food Ingestion After Roux-en-Y Gastric Bypass and the Role of Gut Peptides: A Neuroimaging Study.

PubMed

Hunt, Katharine F; Dunn, Joel T; le Roux, Carel W; Reed, Laurence J; Marsden, Paul K; Patel, Ameet G; Amiel, Stephanie A

2016-10-01

Improved appetite control, possibly mediated by exaggerated gut peptide responses to eating, may contribute to weight loss after Roux-en-Y gastric bypass (RYGB). This study compared brain responses to food ingestion between post-RYGB (RYGB), normal weight (NW), and obese (Ob) unoperated subjects and explored the role of gut peptide responses in RYGB. Neuroimaging with [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography was performed in 12 NW, 21 Ob, and 9 RYGB (18 ± 13 months postsurgery) subjects after an overnight fast, once FED (400 kcal mixed meal), and once FASTED, in random order. RYGB subjects repeated the studies with somatostatin infusion and basal insulin replacement. Fullness, sickness, and postscan ad libitum meal consumption were measured. Regional brain FDG uptake was compared using statistical parametric mapping. RYGB subjects had higher overall fullness and food-induced sickness and lower ad libitum consumption. Brain responses to eating differed in the hypothalamus and pituitary (exaggerated activation in RYGB), left medial orbital cortex (OC) (activation in RYGB, deactivation in NW), right dorsolateral frontal cortex (deactivation in RYGB and NW, absent in Ob), and regions mapping to the default mode network (exaggerated deactivation in RYGB). Somatostatin in RYGB reduced postprandial gut peptide responses, sickness, and medial OC activation. RYGB induces weight loss by augmenting normal brain responses to eating in energy balance regions, restoring lost inhibitory control, and altering hedonic responses. Altered postprandial gut peptide responses primarily mediate changes in food-induced sickness and OC responses, likely to associate with food avoidance. © 2016 by the American Diabetes Association.

Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity.

PubMed

Drew Sayer, R; Tamer, Gregory G; Chen, Ningning; Tregellas, Jason R; Cornier, Marc-Andre; Kareken, David A; Talavage, Thomas M; McCrory, Megan A; Campbell, Wayne W

2016-10-01

The brain's reward system influences ingestive behavior and subsequently obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. This study sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n = 16) and men (n = 12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the two testing days. Mean fasting-state brain responses on day 2 were reduced compared with day 1 in the left insula and right amygdala, but mean day 1 and day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies. © 2016 The Obesity Society.

Music modulation of pain perception and pain-related activity in the brain, brain stem, and spinal cord: a functional magnetic resonance imaging study.

PubMed

Dobek, Christine E; Beynon, Michaela E; Bosma, Rachael L; Stroman, Patrick W

2014-10-01

The oldest known method for relieving pain is music, and yet, to date, the underlying neural mechanisms have not been studied. Here, we investigate these neural mechanisms by applying a well-defined painful stimulus while participants listened to their favorite music or to no music. Neural responses in the brain, brain stem, and spinal cord were mapped with functional magnetic resonance imaging spanning the cortex, brain stem, and spinal cord. Subjective pain ratings were observed to be significantly lower when pain was administered with music than without music. The pain stimulus without music elicited neural activity in brain regions that are consistent with previous studies. Brain regions associated with pleasurable music listening included limbic, frontal, and auditory regions, when comparing music to non-music pain conditions. In addition, regions demonstrated activity indicative of descending pain modulation when contrasting the 2 conditions. These regions include the dorsolateral prefrontal cortex, periaqueductal gray matter, rostral ventromedial medulla, and dorsal gray matter of the spinal cord. This is the first imaging study to characterize the neural response of pain and how pain is mitigated by music, and it provides new insights into the neural mechanism of music-induced analgesia within the central nervous system. This article presents the first investigation of neural processes underlying music analgesia in human participants. Music modulates pain responses in the brain, brain stem, and spinal cord, and neural activity changes are consistent with engagement of the descending analgesia system. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

NASA Astrophysics Data System (ADS)

Yao, Junjie; Xia, Jun; Maslov, Konstantin; Avanaki, Mohammadreza R. N.; Tsytsarev, Vassiliy; Demchenko, Alexei V.; Wang, Lihong V.

2013-03-01

To control the overall action of the body, brain consumes a large amount of energy in proportion to its volume. In humans and many other species, the brain gets most of its energy from oxygen-dependent metabolism of glucose. An abnormal metabolic rate of glucose and/or oxygen usually reflects a diseased status of brain, such as cancer or Alzheimer's disease. We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively unmixed by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. The glucose response amplitude was about half that of the hemodynamic response. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area showed a clear vascular pattern and spread about twice as wide as that of the glucose response. The PACT of mouse brain metabolism was validated by high-resolution open-scalp OR-PAM and fluorescence imaging. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism.

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

PubMed

Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

2018-04-01

Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

Functional divisions for visual processing in the central brain of flying Drosophila

PubMed Central

Weir, Peter T.; Dickinson, Michael H.

2015-01-01

Although anatomy is often the first step in assigning functions to neural structures, it is not always clear whether architecturally distinct regions of the brain correspond to operational units. Whereas neuroarchitecture remains relatively static, functional connectivity may change almost instantaneously according to behavioral context. We imaged panneuronal responses to visual stimuli in a highly conserved central brain region in the fruit fly, Drosophila, during flight. In one substructure, the fan-shaped body, automated analysis revealed three layers that were unresponsive in quiescent flies but became responsive to visual stimuli when the animal was flying. The responses of these regions to a broad suite of visual stimuli suggest that they are involved in the regulation of flight heading. To identify the cell types that underlie these responses, we imaged activity in sets of genetically defined neurons with arborizations in the targeted layers. The responses of this collection during flight also segregated into three sets, confirming the existence of three layers, and they collectively accounted for the panneuronal activity. Our results provide an atlas of flight-gated visual responses in a central brain circuit. PMID:26324910

Functional divisions for visual processing in the central brain of flying Drosophila.

PubMed

Weir, Peter T; Dickinson, Michael H

2015-10-06

Although anatomy is often the first step in assigning functions to neural structures, it is not always clear whether architecturally distinct regions of the brain correspond to operational units. Whereas neuroarchitecture remains relatively static, functional connectivity may change almost instantaneously according to behavioral context. We imaged panneuronal responses to visual stimuli in a highly conserved central brain region in the fruit fly, Drosophila, during flight. In one substructure, the fan-shaped body, automated analysis revealed three layers that were unresponsive in quiescent flies but became responsive to visual stimuli when the animal was flying. The responses of these regions to a broad suite of visual stimuli suggest that they are involved in the regulation of flight heading. To identify the cell types that underlie these responses, we imaged activity in sets of genetically defined neurons with arborizations in the targeted layers. The responses of this collection during flight also segregated into three sets, confirming the existence of three layers, and they collectively accounted for the panneuronal activity. Our results provide an atlas of flight-gated visual responses in a central brain circuit.

Associations between regional brain physiology and trait impulsivity, motor inhibition, and impaired control over drinking

PubMed Central

Weafer, Jessica; Dzemidzic, Mario; Eiler, William; Oberlin, Brandon G.; Wang, Yang; Kareken, David A.

2015-01-01

Trait impulsivity and poor inhibitory control are well-established risk factors for alcohol misuse, yet little is known about the associated neurobiological endophenotypes. Here we examined correlations among brain physiology and self-reported trait impulsive behavior, impaired control over drinking, and a behavioral measure of response inhibition. A sample of healthy drinkers (n=117) completed a pulsed arterial spin labeling (PASL) scan to quantify resting regional cerebral blood flow (rCBF), and measures of self-reported impulsivity (Eysenck I7 Impulsivity scale) and impaired control over drinking. A subset of subjects (n=40) performed a stop signal task during blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to assess brain regions involved in response inhibition. Eysenck I7 scores were inversely related to blood flow in the right precentral gyrus. Significant BOLD activation during response inhibition occurred in an overlapping right frontal motor/premotor region. Moreover, impaired control over drinking was associated with reduced BOLD response in the same region. These findings suggest that impulsive personality and impaired control over drinking are associated with brain physiology in areas implicated in response inhibition. This is consistent with the idea that difficulty controlling behavior is due in part to impairment in motor restraint systems. PMID:26065376

Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents.

PubMed

Jastreboff, Ania M; Sinha, Rajita; Arora, Jagriti; Giannini, Cosimo; Kubat, Jessica; Malik, Saima; Van Name, Michelle A; Santoro, Nicola; Savoye, Mary; Duran, Elvira J; Pierpont, Bridget; Cline, Gary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia

2016-07-01

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Brain Activations Related to Saccadic Response Conflict are not Sensitive to Time on Task.

PubMed

Beldzik, Ewa; Domagalik, Aleksandra; Oginska, Halszka; Marek, Tadeusz; Fafrowicz, Magdalena

2015-01-01

Establishing a role of the dorsal medial frontal cortex in the performance monitoring and cognitive control has been a challenge to neuroscientists for the past decade. In light of recent findings, the conflict monitoring hypothesis has been elaborated to an action-outcome predictor theory. One of the findings that led to this re-evaluation was the fMRI study in which conflict-related brain activity was investigated in terms of the so-called time on task effect, i.e., a linear increase of the BOLD signal with longer response times. The aim of this study was to investigate brain regions involved in the processing of saccadic response conflict and to account for the time on task effect. A modified spatial cueing task was implemented in the event-related fMRI study with oculomotor responses. The results revealed several brain regions which show higher activity for incongruent trials in comparison to the congruent ones, including pre-supplementary motor area together with the frontal and parietal regions. Further analysis accounting for the effect of response time provided evidence that these brain activations were not sensitive to time on task but reflected purely the congruency effect.

Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T.

PubMed

Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; van der Zwaag, Wietske

2018-06-01

External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI. © 2018 Wiley Periodicals, Inc.

Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity

PubMed Central

Sayer, R Drew; Tamer, Gregory G; Chen, Ningning; Tregellas, Jason R; Cornier, Marc-Andre; Kareken, David A; Talavage, Thomas M; McCrory, Megan A; Campbell, Wayne W

2016-01-01

Objective The brain’s reward system influences ingestive behavior and subsequently, obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. We sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. Methods A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n=16) and men (n=12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the 2 testing days. Results Mean fasting-state brain responses on Day 2 were reduced compared to Day 1 in the left insula and right amygdala, but mean Day 1 and Day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. Conclusion fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility, but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies. PMID:27542906

A centric/non-centric impact protocol and finite element model methodology for the evaluation of American football helmets to evaluate risk of concussion.

PubMed

Post, Andrew; Oeur, Anna; Walsh, Evan; Hoshizaki, Blaine; Gilchrist, Michael D

2014-01-01

American football reports high incidences of head injuries, in particular, concussion. Research has described concussion as primarily a rotation dominant injury affecting the diffuse areas of brain tissue. Current standards do not measure how helmets manage rotational acceleration or how acceleration loading curves influence brain deformation from an impact and thus are missing important information in terms of how concussions occur. The purpose of this study was to investigate a proposed three-dimensional impact protocol for use in evaluating football helmets. The dynamic responses resulting from centric and non-centric impact conditions were examined to ascertain the influence they have on brain deformations in different functional regions of the brain that are linked to concussive symptoms. A centric and non-centric protocol was used to impact an American football helmet; the resulting dynamic response data was used in conjunction with a three-dimensional finite element analysis of the human brain to calculate brain tissue deformation. The direction of impact created unique loading conditions, resulting in peaks in different regions of the brain associated with concussive symptoms. The linear and rotational accelerations were not predictive of the brain deformation metrics used in this study. In conclusion, the test protocol used in this study revealed that impact conditions influences the region of loading in functional regions of brain tissue that are associated with the symptoms of concussion. The protocol also demonstrated that using brain deformation metrics may be more appropriate when evaluating risk of concussion than using dynamic response data alone.

Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

PubMed Central

Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li

2013-01-01

Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378

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.

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

Relation of dietary restraint scores to activation of reward-related brain regions in response to food intake, anticipated intake, and food pictures.

PubMed

Burger, Kyle S; Stice, Eric

2011-03-01

Prospective studies indicate that individuals with elevated dietary restraint scores are at increased risk for future bulimic symptom onset, suggesting that these individuals may show hyper-responsivity of reward regions to food and food cues. Thus, we used functional magnetic resonance imaging (fMRI) to examine the relation of dietary restraint scores to activation of reward-related brain regions in response to receipt and anticipated receipt of chocolate milkshake and exposure to pictures of appetizing foods in 39 female adolescents (mean age=15.5 ± 0.94). Dietary restraint scores were positively correlated with activation in the right orbitofrontal cortex (OFC) and bilateral dorsolateral prefrontal cortex (DLPFC) in response to milkshake receipt. However, dietary restraint scores did not correlate with activation in response to anticipated milkshake receipt or exposure to food pictures. Results indicate that individuals who report high dietary restraint have a hyper-responsivity in reward-related brain regions when food intake is occurring, which may increase risk for overeating and binge eating. Copyright © 2010 Elsevier Inc. All rights reserved.

Modality-specific spectral dynamics in response to visual and tactile sequential shape information processing tasks: An MEG study using multivariate pattern classification analysis.

PubMed

Gohel, Bakul; Lee, Peter; Jeong, Yong

2016-08-01

Brain regions that respond to more than one sensory modality are characterized as multisensory regions. Studies on the processing of shape or object information have revealed recruitment of the lateral occipital cortex, posterior parietal cortex, and other regions regardless of input sensory modalities. However, it remains unknown whether such regions show similar (modality-invariant) or different (modality-specific) neural oscillatory dynamics, as recorded using magnetoencephalography (MEG), in response to identical shape information processing tasks delivered to different sensory modalities. Modality-invariant or modality-specific neural oscillatory dynamics indirectly suggest modality-independent or modality-dependent participation of particular brain regions, respectively. Therefore, this study investigated the modality-specificity of neural oscillatory dynamics in the form of spectral power modulation patterns in response to visual and tactile sequential shape-processing tasks that are well-matched in terms of speed and content between the sensory modalities. Task-related changes in spectral power modulation and differences in spectral power modulation between sensory modalities were investigated at source-space (voxel) level, using a multivariate pattern classification (MVPC) approach. Additionally, whole analyses were extended from the voxel level to the independent-component level to take account of signal leakage effects caused by inverse solution. The modality-specific spectral dynamics in multisensory and higher-order brain regions, such as the lateral occipital cortex, posterior parietal cortex, inferior temporal cortex, and other brain regions, showed task-related modulation in response to both sensory modalities. This suggests modality-dependency of such brain regions on the input sensory modality for sequential shape-information processing. Copyright © 2016 Elsevier B.V. All rights reserved.

Modulation of electric brain responses evoked by pitch deviants through transcranial direct current stimulation.

PubMed

Royal, Isabelle; Zendel, Benjamin Rich; Desjardins, Marie-Ève; Robitaille, Nicolas; Peretz, Isabelle

2018-01-31

Congenital amusia is a neurodevelopmental disorder, characterized by a difficulty detecting pitch deviation that is related to abnormal electrical brain responses. Abnormalities found along the right fronto-temporal pathway between the inferior frontal gyrus (IFG) and the auditory cortex (AC) are the likely neural mechanism responsible for amusia. To investigate the causal role of these regions during the detection of pitch deviants, we applied cathodal (inhibitory) transcranial direct current stimulation (tDCS) over right frontal and right temporal regions during separate testing sessions. We recorded participants' electrical brain activity (EEG) before and after tDCS stimulation while they performed a pitch change detection task. Relative to a sham condition, there was a decrease in P3 amplitude after cathodal stimulation over both frontal and temporal regions compared to pre-stimulation baseline. This decrease was associated with small pitch deviations (6.25 cents), but not large pitch deviations (200 cents). Overall, this demonstrates that using tDCS to disrupt regions around the IFG and AC can induce temporary changes in evoked brain activity when processing pitch deviants. These electrophysiological changes are similar to those observed in amusia and provide causal support for the connection between P3 and fronto-temporal brain regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Male and female voices activate distinct regions in the male brain.

PubMed

Sokhi, Dilraj S; Hunter, Michael D; Wilkinson, Iain D; Woodruff, Peter W R

2005-09-01

In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be perceived as gender-specific. Given that functional neuro-imaging correlates of AVHs involve multiple brain regions principally including auditory cortex, it is likely that those brain regions responsible for attribution of gender to speech are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and a paradigm utilising 'gender-apparent' (unaltered) and 'gender-ambiguous' (pitch-scaled) male and female voice stimuli to test the hypothesis that male and female voices activate distinct brain areas during gender attribution. The perception of female voices, when compared with male voices, affected greater activation of the right anterior superior temporal gyrus, near the superior temporal sulcus. Similarly, male voice perception activated the mesio-parietal precuneus area. These different gender associations could not be explained by either simple pitch perception or behavioural response because the activations that we observed were conjointly activated by both 'gender-apparent' and 'gender-ambiguous' voices. The results of this study demonstrate that, in the male brain, the perception of male and female voices activates distinct brain regions.

Characterizing the Associative Content of Brain Structures Involved in Habitual and Goal-Directed Actions in Humans: A Multivariate fMRI Study

PubMed Central

Liljeholm, Mimi; Zika, Ondrej; O'Doherty, John P.

2015-01-01

While there is accumulating evidence for the existence of distinct neural systems supporting goal-directed and habitual action selection in the mammalian brain, much less is known about the nature of the information being processed in these different brain regions. Associative learning theory predicts that brain systems involved in habitual control, such as the dorsolateral striatum, should contain stimulus and response information only, but not outcome information, while regions involved in goal-directed action, such as ventromedial and dorsolateral prefrontal cortex and dorsomedial striatum, should be involved in processing information about outcomes as well as stimuli and responses. To test this prediction, human participants underwent fMRI while engaging in a binary choice task designed to enable the separate identification of these different representations with a multivariate classification analysis approach. Consistent with our predictions, the dorsolateral striatum contained information about responses but not outcomes at the time of an initial stimulus, while the regions implicated in goal-directed action selection contained information about both responses and outcomes. These findings suggest that differential contributions of these regions to habitual and goal-directed behavioral control may depend in part on basic differences in the type of information that these regions have access to at the time of decision making. PMID:25740507

Brain mediators of predictive cue effects on perceived pain

PubMed Central

Atlas, Lauren Y.; Bolger, Niall; Lindquist, Martin A.; Wager, Tor D.

2010-01-01

Information about upcoming pain strongly influences pain experience in experimental and clinical settings, but little is known about the brain mechanisms that link expectation and experience. To identify the pathways by which informational cues influence perception, analyses must jointly consider both the effects of cues on brain responses and the relationship between brain responses and changes in reported experience. Our task and analysis strategy were designed to test these relationships. Auditory cues elicited expectations for low or high painful thermal stimulation, and we assessed how cues influenced human subjects’ pain reports and BOLD fMRI responses to matched levels of noxious heat. We used multi-level mediation analysis to identify brain regions that 1) are modulated by predictive cues, 2) predict trial-to-trial variations in pain reports, and 3) formally mediate the relationship between cues and reported pain. Cues influenced heat-evoked responses in most canonical pain-processing regions, including both medial and lateral pain pathways. Effects on several regions correlated with pre-task expectations, suggesting that expectancy plays a prominent role. A subset of pain-processing regions, including anterior cingulate cortex, anterior insula, and thalamus, formally mediated cue effects on pain. Effects on these regions were in turn mediated by cue-evoked anticipatory activity in the medial orbitofrontal cortex (OFC) and ventral striatum, areas not previously directly implicated in nociception. These results suggest that activity in pain-processing regions reflects a combination of nociceptive input and top-down information related to expectations, and that anticipatory processes in OFC and striatum may play a key role in modulating pain processing. PMID:20881115

Brain Activity in Self- and Value-Related Regions in Response to Online Antismoking Messages Predicts Behavior Change

PubMed Central

Cooper, Nicole; Tompson, Steve; O’Donnell, Matthew Brook; Falk, Emily B.

2017-01-01

In this study, we combined approaches from media psychology and neuroscience to ask whether brain activity in response to online antismoking messages can predict smoking behavior change. In particular, we examined activity in subregions of the medial prefrontal cortex linked to self- and value-related processing, to test whether these neurocognitive processes play a role in message-consistent behavior change. We observed significant relationships between activity in both brain regions of interest and behavior change (such that higher activity predicted a larger reduction in smoking). Furthermore, activity in these brain regions predicted variance independent of traditional, theory-driven self-report metrics such as intention, self-efficacy, and risk perceptions. We propose that valuation is an additional cognitive process that should be investigated further as we search for a mechanistic explanation of the relationship between brain activity and media effects relevant to health behavior change. PMID:29057013

Regional entropy of functional imaging signals varies differently in sensory and cognitive systems during propofol-modulated loss and return of behavioral responsiveness.

PubMed

Liu, Xiaolin; Lauer, Kathryn K; Ward, B Douglas; Roberts, Christopher J; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Xu, Zhan; Chen, Shanshan; Wang, Lubin; Yang, Zheng; Li, Shi-Jiang; Binder, Jeffrey R; Hudetz, Anthony G

2018-05-08

The level and richness of consciousness depend on information integration in the brain. Altered interregional functional interactions may indicate disrupted information integration during anesthetic-induced unconsciousness. How anesthetics modulate the amount of information in various brain regions has received less attention. Here, we propose a novel approach to quantify regional information content in the brain by the entropy of the principal components of regional blood oxygen-dependent imaging signals during graded propofol sedation. Fifteen healthy individuals underwent resting-state scans in wakeful baseline, light sedation (conscious), deep sedation (unconscious), and recovery (conscious). Light sedation characterized by lethargic behavioral responses was associated with global reduction of entropy in the brain. Deep sedation with completely suppressed overt responsiveness was associated with further reductions of entropy in sensory (primary and higher sensory plus orbital prefrontal cortices) but not high-order cognitive (dorsal and medial prefrontal, cingulate, parietotemporal cortices and hippocampal areas) systems. Upon recovery of responsiveness, entropy was restored in the sensory but not in high-order cognitive systems. These findings provide novel evidence for a reduction of information content of the brain as a potential systems-level mechanism of reduced consciousness during propofol anesthesia. The differential changes of entropy in the sensory and high-order cognitive systems associated with losing and regaining overt responsiveness are consistent with the notion of "disconnected consciousness", in which a complete sensory-motor disconnection from the environment occurs with preserved internal mentation.

Exploring time- and frequency- dependent functional connectivity and brain networks during deception with single-trial event-related potentials

NASA Astrophysics Data System (ADS)

Gao, Jun-Feng; Yang, Yong; Huang, Wen-Tao; Lin, Pan; Ge, Sheng; Zheng, Hong-Mei; Gu, Ling-Yun; Zhou, Hui; Li, Chen-Hong; Rao, Ni-Ni

2016-11-01

To better characterize the cognitive processes and mechanisms that are associated with deception, wavelet coherence was employed to evaluate functional connectivity between different brain regions. Two groups of subjects were evaluated for this purpose: 32 participants were required to either tell the truth or to lie when facing certain stimuli, and their electroencephalogram signals on 12 electrodes were recorded. The experimental results revealed that deceptive responses elicited greater connectivity strength than truthful responses, particularly in the θ band on specific electrode pairs primarily involving connections between the prefrontal/frontal and central regions and between the prefrontal/frontal and left parietal regions. These results indicate that these brain regions play an important role in executing lying responses. Additionally, three time- and frequency-dependent functional connectivity networks were proposed to thoroughly reflect the functional coupling of brain regions that occurs during lying. Furthermore, the wavelet coherence values for the connections shown in the networks were extracted as features for support vector machine training. High classification accuracy suggested that the proposed network effectively characterized differences in functional connectivity between the two groups of subjects over a specific time-frequency area and hence could be a sensitive measurement for identifying deception.

Proteomic Analysis of Mouse Hypothalamus under Simulated Microgravity

PubMed Central

Sarkar, Poonam; Sarkar, Shubhashish; Ramesh, Vani; Kim, Helen; Barnes, Stephen; Kulkarni, Anil; Hall, Joseph C.; Wilson, Bobby L.; Thomas, Renard L.; Pellis, Neal R.

2009-01-01

Exposure to altered microgravity during space travel induces changes in the brain and these are reflected in many of the physical behavior seen in the astronauts. The vulnerability of the brain to microgravity stress has been reviewed and reported. Identifying microgravity-induced changes in the brain proteome may aid in understanding the impact of the microgravity environment on brain function. In our previous study we have reported changes in specific proteins under simulated microgravity in the hippocampus using proteomics approach. In the present study the profiling of the hypothalamus region in the brain was studied as a step towards exploring the effect of microgravity in this region of the brain. Hypothalamus is the critical region in the brain that strictly controls the pituitary gland that in turn is responsible for the secretion of important hormones. Here we report a 2-dimensional gel electrophoretic analysis of the mouse hypothalamus in response to simulated microgravity. Lowered glutathione and differences in abundance expression of seven proteins were detected in the hypothalamus of mice exposed to microgravity. These changes included decreased superoxide dismutase-2 (SOD-2) and increased malate dehydrogenase and peroxiredoxin-6, reflecting reduction of the antioxidant system in the hypothalamus. Taken together the results reported here indicate that oxidative imbalance occurred in the hypothalamus in response to simulated microgravity. PMID:18473167

Cerebral control of the bladder in normal and urge-incontinent women

PubMed Central

Griffiths, Derek; Tadic, Stasa D.; Schaefer, Werner; Resnick, Neil M.

2007-01-01

Aim: To identify age-related changes in the normal brain/bladder control system, and differences between urge incontinence in younger and older women, as shown by brain responses to bladder filling; and to use age, bladder volume, urge incontinence and detrusor overactivity (DO) as probes to reveal control-system function. Functional MRI was used to examine regional brain responses to bladder infusion in 21 females (26 – 85 years): 11 “cases” with urge incontinence and DO (proven previously) and 10 normal “controls”. Responses and their age dependence were determined at small and large bladder volumes, in whole brain and in regions of interest representing right insula and anterior cingulate (ACG). In “controls”, increasing bladder volume/sensation led to increasing insular responses; with increasing age, insular responses became weaker. In younger “cases”, ACG responded abnormally strongly at large bladder volumes/strong sensation. Elderly “cases” showed strong ACG responses even at small bladder volume, but more moderate responses at larger volumes; if DO occurred, pontine micturition center (PMC) activation did not increase. Conclusion: Among normal “controls”, increasing age leads to decreased responses in brain regions involved in bladder control, including right insula, consistent with its role in mapping normal bladder sensations. Strong ACG activation occurs in urge-incontinent “cases” and may be a sign of urgency, indicating recruitment of alternative pathways when loss of bladder control is feared. Easier ACG provocation in older “cases” reflects lack of physiological reserve or different etiology. ACG responses seem associated with PMC inhibition: reduced ACG activity accompanies failure of inhibition (DO). PMID:17574871

Reduced evoked fos expression in activity-related brain regions in animal models of behavioral depression.

PubMed

Stone, Eric A; Lehmann, Michael L; Lin, Yan; Quartermain, David

2007-08-15

A previous study showed that two mouse models of behavioral depression, immune system activation and depletion of brain monoamines, are accompanied by marked reductions in stimulated neural activity in brain regions involved in motivated behavior. The present study tested whether this effect is common to other depression models by examining the effects of repeated forced swimming, chronic subordination stress or acute intraventricular galanin injection - three additional models - on baseline or stimulated c-fos expression in several brain regions known to be involved in motor or motivational processes (secondary motor, M2, anterior piriform cortex, APIR, posterior cingulate gyrus, CG, nucleus accumbens, NAC). Each of the depression models was found to reduce the fos response stimulated by exposure to a novel cage or a swim stress in all four of these brain areas but not to affect the response of a stress-sensitive region (paraventricular hypothalamus, PVH) that was included for control purposes. Baseline fos expression in these structures was either unaffected or affected in an opposite direction to the stimulated response. Pretreatment with either desmethylimipramine (DMI) or tranylcypromine (tranyl) attenuated these changes. It is concluded that the pattern of a reduced neural function of CNS motor/motivational regions with an increased function of stress areas is common to 5 models of behavioral depression in the mouse and is a potential experimental analog of the neural activity changes occurring in the clinical condition.

Patterns of neural activity associated with differential acute locomotor stimulation to cocaine and methamphetamine in adolescent versus adult male C57BL/6J mice

PubMed Central

Zombeck, Jonathan A.; Lewicki, Aaron D.; Patel, Kevin; Gupta, Tripta; Rhodes, Justin S.

2009-01-01

Adolescence is a time period when major changes occur in the brain with long-term consequences for behavior. One ramification is altered responses to drugs of abuse, but the specific brain mechanisms and implications for mental health are poorly understood. Here, we used a mouse model in which adolescents display dramatically reduced sensitivity to the acute locomotor stimulating effects of cocaine and methamphetamine. The goal was to identify key brain regions or circuits involved in the differential behavior. Male adolescent (PN 30–35) and young adult (PN 69–74) C57BL/6J mice were administered an intraperitoneal injection of cocaine (0, 15, 30 mg/kg) or methamphetamine (0, 2, 4 mg/kg) and euthanized 90 minutes later. Locomotor activity was monitored continuously in the home cage by video tracking. Immunohistochemical detection of Fos protein was used to quantify neuronal activation in 16 different brain regions. As expected, adolescents were less sensitive to the locomotor stimulating effects of cocaine and methamphetamine as indicated by a rightward shift in the dose response relationship. After a saline injection, adolescents showed similar levels of Fos as adults in all regions except the dorsal and lateral caudate where levels were lower in adolescents. Cocaine and methamphetamine dose dependently increased Fos in all brain regions sampled in both adolescents and adults, but Fos levels were similar in both age groups for a majority of regions and doses. Locomotor activity was correlated with Fos in several brain areas within adolescent and adult groups, and adolescents had a significantly greater induction of Fos for a given amount of locomotor activity in key brain regions including the caudate where they showed reduced Fos under baseline conditions. Future research will identify the molecular and cellular events that are responsible for the differential psychostimulant-induced patterns of brain activation and behavior observed in adolescent versus adult mice. PMID:19932887

Diffusion of responsibility attenuates altruistic punishment: A functional magnetic resonance imaging effective connectivity study.

PubMed

Feng, Chunliang; Deshpande, Gopikrishna; Liu, Chao; Gu, Ruolei; Luo, Yue-Jia; Krueger, Frank

2016-02-01

Humans altruistically punish violators of social norms to enforce cooperation and pro-social behaviors. However, such altruistic behaviors diminish when others are present, due to a diffusion of responsibility. We investigated the neural signatures underlying the modulations of diffusion of responsibility on altruistic punishment, conjoining a third-party punishment task with event-related functional magnetic resonance imaging and multivariate Granger causality mapping. In our study, participants acted as impartial third-party decision-makers and decided how to punish norm violations under two different social contexts: alone (i.e., full responsibility) or in the presence of putative other third-party decision makers (i.e., diffused responsibility). Our behavioral results demonstrated that the diffusion of responsibility served as a mediator of context-dependent punishment. In the presence of putative others, participants who felt less responsible also punished less severely in response to norm violations. Our neural results revealed that underlying this behavioral effect was a network of interconnected brain regions. For unfair relative to fair splits, the presence of others led to attenuated responses in brain regions implicated in signaling norm violations (e.g., AI) and to increased responses in brain regions implicated in calculating values of norm violations (e.g., vmPFC, precuneus) and mentalizing about others (dmPFC). The dmPFC acted as the driver of the punishment network, modulating target regions, such as AI, vmPFC, and precuneus, to adjust altruistic punishment behavior. Our results uncovered the neural basis of the influence of diffusion of responsibility on altruistic punishment and highlighted the role of the mentalizing network in this important phenomenon. Hum Brain Mapp 37:663-677, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Regional TNFα mapping in the brain reveals the striatum as a neuroinflammatory target after ventricular fibrillation cardiac arrest in rats☆

PubMed Central

Janata, Andreas; Magnet, Ingrid A.M.; Uray, Thomas; Stezoski, Jason P.; Janesko-Feldman, Keri; Tisherman, Samuel A.; Kochanek, Patrick M.; Drabek, Tomas

2014-01-01

Cardiac arrest (CA) triggers neuroinflammation that could play a role in a delayed neuronal death. In our previously established rat model of ventricular fibrillation (VF) CA characterized by extensive neuronal death, we tested the hypothesis that individual brain regions have specific neuroinflammatory responses, as reflected by regional brain tissue levels of tumor necrosis factor (TNF)α and other cytokines. In a prospective study, rats were randomized to 6 min (CA6), 8 min (CA8) or 10 min (CA10) of VF CA, or sham group. Cortex, striatum, hippocampus and cerebellum were evaluated for TNFα and interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12 and interferon gamma at 3 h, 6 h or 14 d after CA by ELISA and Luminex. Immunohistochemistry was used to determine the cell source of TNFα. CA resulted in a selective TNFα response with significant regional and temporal differences. At 3 h after CA, TNFα-levels increased in all regions depending on the duration of the insult. The most pronounced increase was observed in striatum that showed 20-fold increase in CA10 vs. sham, and 3-fold increase vs. CA6 or CA8 group, respectively (p < 0.01). TNFα levels in striatum decreased between 3 h and 6 h, but increased in other regions between 3 h and 14 d. TNFα levels remained twofold higher in CA6 vs. shams across brain regions at 14 d (p < 0.01). In contrast to pronounced TNFα response, other cytokines showed only a minimal increase in CA6 and CA8 groups vs. sham in all brain regions with the exception that IL-1β increased twofold in cerebellum and striatum (p < 0.01). TNFα colocalized with neurons. In conclusion, CA produced a duration-dependent acute TNFα response, with dramatic increase in the striatum where TNFα colocalized with neurons. Increased TNFα levels persist for at least two weeks. This TNFα surge contrasts the lack of an acute increase in other cytokines in brain after CA. Given that striatum is a selectively vulnerable brain region, our data suggest possible role of neuronal TNFα in striatum after CA and identify therapeutic targets for future experiments. PMID:24530249

Characterizing the associative content of brain structures involved in habitual and goal-directed actions in humans: a multivariate FMRI study.

PubMed

McNamee, Daniel; Liljeholm, Mimi; Zika, Ondrej; O'Doherty, John P

2015-03-04

While there is accumulating evidence for the existence of distinct neural systems supporting goal-directed and habitual action selection in the mammalian brain, much less is known about the nature of the information being processed in these different brain regions. Associative learning theory predicts that brain systems involved in habitual control, such as the dorsolateral striatum, should contain stimulus and response information only, but not outcome information, while regions involved in goal-directed action, such as ventromedial and dorsolateral prefrontal cortex and dorsomedial striatum, should be involved in processing information about outcomes as well as stimuli and responses. To test this prediction, human participants underwent fMRI while engaging in a binary choice task designed to enable the separate identification of these different representations with a multivariate classification analysis approach. Consistent with our predictions, the dorsolateral striatum contained information about responses but not outcomes at the time of an initial stimulus, while the regions implicated in goal-directed action selection contained information about both responses and outcomes. These findings suggest that differential contributions of these regions to habitual and goal-directed behavioral control may depend in part on basic differences in the type of information that these regions have access to at the time of decision making. Copyright © 2015 the authors 0270-6474/15/353764-08$15.00/0.

Overdrinking, swallowing inhibition, and regional brain responses prior to swallowing

PubMed Central

Saker, Pascal; Egan, Gary F.; McKinley, Michael J.; Denton, Derek A.

2016-01-01

In humans, drinking replenishes fluid loss and satiates the sensation of thirst that accompanies dehydration. Typically, the volume of water drunk in response to thirst matches the deficit. Exactly how this accurate metering is achieved is unknown; recent evidence implicates swallowing inhibition as a potential factor. Using fMRI, this study investigated whether swallowing inhibition is present after more water has been drunk than is necessary to restore fluid balance within the body. This proposal was tested using ratings of swallowing effort and measuring regional brain responses as participants prepared to swallow small volumes of liquid while they were thirsty and after they had overdrunk. Effort ratings provided unequivocal support for swallowing inhibition, with a threefold increase in effort after overdrinking, whereas addition of 8% (wt/vol) sucrose to water had minimal effect on effort before or after overdrinking. Regional brain responses when participants prepared to swallow showed increases in the motor cortex, prefrontal cortices, posterior parietal cortex, striatum, and thalamus after overdrinking, relative to thirst. Ratings of swallowing effort were correlated with activity in the right prefrontal cortex and pontine regions in the brainstem; no brain regions showed correlated activity with pleasantness ratings. These findings are all consistent with the presence of swallowing inhibition after excess water has been drunk. We conclude that swallowing inhibition is an important mechanism in the overall regulation of fluid intake in humans. PMID:27791015

Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome.

PubMed

Mutch, W Alan C; Ellis, Michael J; Ryner, Lawrence N; Ruth Graham, M; Dufault, Brenden; Gregson, Brian; Hall, Thomas; Bunge, Martin; Essig, Marco; Fisher, Joseph A; Duffin, James; Mikulis, David J

2016-09-01

OBJECT A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow (CBF) and cerebrovascular responsiveness in individual patients with concussion remains elusive. Here the authors summarize the safety, feasibility, and results of brain CO2 stress testing in adolescents with postconcussion syndrome (PCS) and healthy controls. METHODS This study was approved by the Biomedical Research Ethics Board at the University of Manitoba. Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI, pseudo-continuous arterial spin labeling MRI, and brain stress testing using controlled CO2 challenge and blood oxygen level-dependent (BOLD) MRI. Post hoc processing was performed using statistical parametric mapping to determine voxel-by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO2 stimulus (increase in BOLD signal) or the inverse (decrease in BOLD signal). Receiver operating characteristic (ROC) curves were generated to compare voxel counts categorized by control (0) or PCS (1). RESULTS Studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study participants. No differences in CO2 stimuli were seen between the 2 participant groups. No group differences in global mean CBF were detected between PCS patients and healthy controls. Patient-specific differences in mean regional CBF and CO2 BOLD responsiveness were observed in all PCS patients. The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas (that is, abnormal voxel counts) produced an area under the curve of 0.87 (p < 0.0001) and 0.80 (p = 0.0003), respectively, consistent with a clinically useful predictive model. CONCLUSIONS Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF. Future prospective studies are warranted to examine the utility of brain MRI CO2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS.

Spatio-Temporal Information Analysis of Event-Related BOLD Responses

PubMed Central

Alpert, Galit Fuhrmann; Handwerker, Dan; Sun, Felice T.; D’Esposito, Mark; Knight, Robert T.

2009-01-01

A new approach for analysis of event related fMRI (BOLD) signals is proposed. The technique is based on measures from information theory and is used both for spatial localization of task related activity, as well as for extracting temporal information regarding the task dependent propagation of activation across different brain regions. This approach enables whole brain visualization of voxels (areas) most involved in coding of a specific task condition, the time at which they are most informative about the condition, as well as their average amplitude at that preferred time. The approach does not require prior assumptions about the shape of the hemodynamic response function (HRF), nor about linear relations between BOLD response and presented stimuli (or task conditions). We show that relative delays between different brain regions can also be computed without prior knowledge of the experimental design, suggesting a general method that could be applied for analysis of differential time delays that occur during natural, uncontrolled conditions. Here we analyze BOLD signals recorded during performance of a motor learning task. We show that during motor learning, the BOLD response of unimodal motor cortical areas precedes the response in higher-order multimodal association areas, including posterior parietal cortex. Brain areas found to be associated with reduced activity during motor learning, predominantly in prefrontal brain regions, are informative about the task typically at significantly later times. PMID:17188515

Prolonged hemodynamic response during incidental facial emotion processing in inter-episode bipolar I disorder.

PubMed

Rosenfeld, Ethan S; Pearlson, Godfrey D; Sweeney, John A; Tamminga, Carol A; Keshavan, Matcheri S; Nonterah, Camilla; Stevens, Michael C

2014-03-01

This fMRI study examined whether hemodynamic responses to affectively-salient stimuli were abnormally prolonged in remitted bipolar disorder, possibly representing a novel illness biomarker. A group of 18 DSM-IV bipolar I-diagnosed adults in remission and a demographically-matched control group performed an event-related fMRI gender-discrimination task in which face stimuli had task-irrelevant neutral, happy or angry expressions designed to elicit incidental emotional processing. Participants' brain activation was modeled using a "fully informed" SPM5 basis set. Mixed-model ANOVA tested for diagnostic group differences in BOLD response amplitude and shape within brain regions-of-interest selected from ALE meta-analysis of previous comparable fMRI studies. Bipolar-diagnosed patients had a generally longer duration and/or later-peaking hemodynamic response in amygdala and numerous prefrontal cortex brain regions. Data are consistent with existing models of bipolar limbic hyperactivity, but the prolonged frontolimbic response more precisely details abnormalities recognized in previous studies. Prolonged hemodynamic responses were unrelated to stimulus type, task performance, or degree of residual mood symptoms, suggesting an important novel trait vulnerability brain dysfunction in bipolar disorder. Bipolar patients also failed to engage pregenual cingulate and left orbitofrontal cortex-regions important to models of automatic emotion regulation-while engaging a delayed dorsolateral prefrontal cortex response not seen in controls. These results raise questions about whether there are meaningful relationships between bipolar dysfunction of specific ventromedial prefrontal cortex regions believed to automatically regulate emotional reactions and the prolonged responses in more lateral aspects of prefrontal cortex.

Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala and ventral striatum

PubMed Central

Fletcher, PC; Napolitano, A; Skeggs, A; Miller, SR; Delafont, B; Cambridge, VC; de Wit, S; Nathan, PJ; Brooke, A; O’Rahilly, S; Farooqi, IS; Bullmore, ET

2012-01-01

We used fMRI to explore brain responses to food images in overweight humans, examining independently the impact of a pre-scan meal (“satiety”) and the anti-obesity drug sibutramine, a serotonin and noradrenaline reuptake inhibitor. We identified significantly different responses to these manipulations in amygdala, hypothalamus and ventral striatum. Each region was specifically responsive to high calorie compared to low calorie food images. However, the ventral striatal response was attenuated by satiety (but unaffected by sibutramine) while the hypothalamic and amygdala responses were attenuated by drug but unaffected by satiety. Direct assessment of regional interactions confirmed the significance of this double dissociation. We explored the regional responses in greater detail by determining whether they were predictive of eating behaviour and weight change. We observed that across the different regions, the individual-specific magnitude of drug- and satiety-induced modulation was associated with both variables: the sibutramine-induced modulation of the hypothalamic response was correlated with the drug’s impact on both weight and subsequently-measured ad libitum eating. The satiety-induced modulation of striatal response also correlated with subsequent ad lib eating. These results suggest that hypothalamus and amygdala have roles in the control of food intake that are distinct from those of ventral striatum. Furthermore, they support a regionally-specific effect on brain function through which sibutramine exerts its clinical effect. PMID:20980590

Evidence for hubs in human functional brain networks

PubMed Central

Power, Jonathan D; Schlaggar, Bradley L; Lessov-Schlaggar, Christina N; Petersen, Steven E

2013-01-01

Summary Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting state functional connectivity MRI reports have implicated regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: 1) finding network nodes that participate in multiple sub-networks of the brain, and 2) finding spatial locations where several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity. PMID:23972601

Measurement and Analysis of Olfactory Responses with the Aim of Establishing an Objective Diagnostic Method for Central Olfactory Disorders

NASA Astrophysics Data System (ADS)

Uno, Tominori; Wang, Li-Qun; Miwakeichi, Fumikazu; Tonoike, Mitsuo; Kaneda, Teruo

In order to establish a new diagnostic method for central olfactory disorders and to identify objective indicators, we measured and analyzed brain activities in the parahippocampal gyrus and uncus, region of responsibility for central olfactory disorders. The relationship between olfactory stimulation and brain response at region of responsibility can be examined in terms of fitted responses (FR). FR in these regions may be individual indicators of changes in brain olfactory responses. In the present study, in order to non-invasively and objectively measure olfactory responses, an odor oddball task was conducted on four healthy volunteers using functional magnetic resonance imaging (fMRI) and a odorant stimulator with blast-method. The results showed favorable FR and activation in the parahippocampal gyrus or uncus in all subjects. In some subjects, both the parahippocampal gyrus and uncus were activated. Furthermore, activation was also confirmed in the cingulate gyrus, middle frontal gyrus, precentral gyrus, postcentral gyrus, superior temporal gyrus and insula. The hippocampus and uncus are known to be involved in the olfactory disorders associated with early-stage Alzheimer's disease and other olfactory disorders. In the future, it will be necessary to further develop the present measurement and analysis method to clarify the relationship between central olfactory disorders and brain activities and establish objective indicators that are useful for diagnosis.

Alteration of brain activation patterns in nonallergic rhinitis patients using functional magnetic resonance imaging before and after treatment with intranasal azelastine.

PubMed

Bernstein, Jonathan A; Hastings, Lloyd; Boespflug, Erin L; Allendorfer, Jane B; Lamy, Martine; Eliassen, James C

2011-06-01

Although nonallergic rhinitis (NAR) patients tend to be more sensitive to chemical/olfactory stimuli, a suprathreshold olfactory response or the presence of specific olfactory receptor genes do not explain why their symptoms are triggered by such exposures. To investigate differential neurogenic responses to azelastine in NAR patients, using functional magnetic resonance imaging (fMRI) in response to specific olfactory triggers. A longitudinal study design on 12 subjects with a physician diagnosis of NAR previously demonstrated to be clinically responsive to intranasal azelastine (Astelin) was performed. Subjects underwent fMRI during exposure to unpleasant (hickory smoke) and pleasant (vanilla) odorants while off and then on azelastine for 2 weeks. The olfactory fMRI paradigm consisted of a visually triggered sniff every 21 seconds with synchronized delivery of a 4 second pulse of odorant. Each odorant was presented 18 times over 4-6-minute fMRI runs. Continuous fresh air was presented to wash out each odorant after presentation. Nonallergic rhinitis patients exhibited increased blood flow to several regions of the brain in response to both pleasant and unpleasant odorants, specifically in odor-sensitive regions, while off intranasal azelastine. Treatment with intranasal azelastine significantly attenuated blood flow to regions of the brain relevant to either olfactory sensation or sensory processing in response to these odorants compared with fresh air. The general reduction compared with increase in brain activation in NAR patients on versus off azelastine suggests that a possible effect of this medication may be reduction of brain responses to odorants. Copyright © 2011. Published by Elsevier Inc.

A trade-off between local and distributed information processing associated with remote episodic versus semantic memory.

PubMed

Heisz, Jennifer J; Vakorin, Vasily; Ross, Bernhard; Levine, Brian; McIntosh, Anthony R

2014-01-01

Episodic memory and semantic memory produce very different subjective experiences yet rely on overlapping networks of brain regions for processing. Traditional approaches for characterizing functional brain networks emphasize static states of function and thus are blind to the dynamic information processing within and across brain regions. This study used information theoretic measures of entropy to quantify changes in the complexity of the brain's response as measured by magnetoencephalography while participants listened to audio recordings describing past personal episodic and general semantic events. Personal episodic recordings evoked richer subjective mnemonic experiences and more complex brain responses than general semantic recordings. Critically, we observed a trade-off between the relative contribution of local versus distributed entropy, such that personal episodic recordings produced relatively more local entropy whereas general semantic recordings produced relatively more distributed entropy. Changes in the relative contributions of local and distributed entropy to the total complexity of the system provides a potential mechanism that allows the same network of brain regions to represent cognitive information as either specific episodes or more general semantic knowledge.

Reorganization of Functional Connectivity as a Correlate of Cognitive Recovery in Acquired Brain Injury

ERIC Educational Resources Information Center

Castellanos, Nazareth P.; Paul, Nuria; Ordonez, Victoria E.; Demuynck, Olivier; Bajo, Ricardo; Campo, Pablo; Bilbao, Alvaro; Ortiz, Tomas; del-Pozo, Francisco; Maestu, Fernando

2010-01-01

Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on…

Distinct representations of configural and part information across multiple face-selective regions of the human brain

PubMed Central

Golarai, Golijeh; Ghahremani, Dara G.; Eberhardt, Jennifer L.; Gabrieli, John D. E.

2015-01-01

Several regions of the human brain respond more strongly to faces than to other visual stimuli, such as regions in the amygdala (AMG), superior temporal sulcus (STS), and the fusiform face area (FFA). It is unclear if these brain regions are similar in representing the configuration or natural appearance of face parts. We used functional magnetic resonance imaging of healthy adults who viewed natural or schematic faces with internal parts that were either normally configured or randomly rearranged. Response amplitudes were reduced in the AMG and STS when subjects viewed stimuli whose configuration of parts were digitally rearranged, suggesting that these regions represent the 1st order configuration of face parts. In contrast, response amplitudes in the FFA showed little modulation whether face parts were rearranged or if the natural face parts were replaced with lines. Instead, FFA responses were reduced only when both configural and part information were reduced, revealing an interaction between these factors, suggesting distinct representation of 1st order face configuration and parts in the AMG and STS vs. the FFA. PMID:26594191

Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain

NASA Astrophysics Data System (ADS)

Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

1998-12-01

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

A sLORETA study for gaze-independent BCI speller.

PubMed

Xingwei An; Jinwen Wei; Shuang Liu; Dong Ming

2017-07-01

EEG-based BCI (brain-computer-interface) speller, especially gaze-independent BCI speller, has become a hot topic in recent years. It provides direct spelling device by non-muscular method for people with severe motor impairments and with limited gaze movement. Brain needs to conduct both stimuli-driven and stimuli-related attention in fast presented BCI paradigms for such BCI speller applications. Few researchers studied the mechanism of brain response to such fast presented BCI applications. In this study, we compared the distribution of brain activation in visual, auditory, and audio-visual combined stimuli paradigms using sLORETA (standardized low-resolution brain electromagnetic tomography). Between groups comparisons showed the importance of visual and auditory stimuli in audio-visual combined paradigm. They both contribute to the activation of brain regions, with visual stimuli being the predominate stimuli. Visual stimuli related brain region was mainly located at parietal and occipital lobe, whereas response in frontal-temporal lobes might be caused by auditory stimuli. These regions played an important role in audio-visual bimodal paradigms. These new findings are important for future study of ERP speller as well as the mechanism of fast presented stimuli.

Structural and functional correlates of visual field asymmetry in the human brain by diffusion kurtosis MRI and functional MRI.

PubMed

O'Connell, Caitlin; Ho, Leon C; Murphy, Matthew C; Conner, Ian P; Wollstein, Gadi; Cham, Rakie; Chan, Kevin C

2016-11-09

Human visual performance has been observed to show superiority in localized regions of the visual field across many classes of stimuli. However, the underlying neural mechanisms remain unclear. This study aims to determine whether the visual information processing in the human brain is dependent on the location of stimuli in the visual field and the corresponding neuroarchitecture using blood-oxygenation-level-dependent functional MRI (fMRI) and diffusion kurtosis MRI, respectively, in 15 healthy individuals at 3 T. In fMRI, visual stimulation to the lower hemifield showed stronger brain responses and larger brain activation volumes than the upper hemifield, indicative of the differential sensitivity of the human brain across the visual field. In diffusion kurtosis MRI, the brain regions mapping to the lower visual field showed higher mean kurtosis, but not fractional anisotropy or mean diffusivity compared with the upper visual field. These results suggested the different distributions of microstructural organization across visual field brain representations. There was also a strong positive relationship between diffusion kurtosis and fMRI responses in the lower field brain representations. In summary, this study suggested the structural and functional brain involvements in the asymmetry of visual field responses in humans, and is important to the neurophysiological and psychological understanding of human visual information processing.

Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress.

PubMed

Vialou, Vincent; Thibault, Mackenzie; Kaska, Sophia; Cooper, Sarah; Gajewski, Paula; Eagle, Andrew; Mazei-Robison, Michelle; Nestler, Eric J; Robison, A J

2015-12-01

Major depressive disorder is thought to arise in part from dysfunction of the brain's "reward circuitry", consisting of the mesolimbic dopamine system and the glutamatergic and neuromodulatory inputs onto this system. Both chronic stress and antidepressant treatment regulate gene transcription in many of the brain regions that make up these circuits, but the exact nature of the transcription factors and target genes involved in these processes remain unclear. Here, we demonstrate induction of the FosB family of transcription factors in ∼25 distinct regions of adult mouse brain, including many parts of the reward circuitry, by chronic exposure to the antidepressant fluoxetine. We further uncover specific patterns of FosB gene product expression (i.e., differential expression of full-length FosB, ΔFosB, and Δ2ΔFosB) in brain regions associated with depression--the nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus--in response to chronic fluoxetine treatment, and contrast these patterns with differential induction of FosB isoforms in the chronic social defeat stress model of depression with and without fluoxetine treatment. We find that chronic fluoxetine, in contrast to stress, causes induction of the unstable full-length FosB isoform in the NAc, PFC, and hippocampus even 24 h following the final injection, indicating that these brain regions may undergo chronic activation when fluoxetine is on board, even in the absence of stress. We also find that only the stable ΔFosB isoform correlates with behavioral responses to stress. These data suggest that NAc, PFC, and hippocampus may present useful targets for directed intervention in mood disorders (ie, brain stimulation or gene therapy), and that determining the gene targets of FosB-mediated transcription in these brain regions in response to fluoxetine may yield novel inroads for pharmaceutical intervention in depressive disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

fMRI during natural sleep as a method to study brain function during early childhood.

PubMed

Redcay, Elizabeth; Kennedy, Daniel P; Courchesne, Eric

2007-12-01

Many techniques to study early functional brain development lack the whole-brain spatial resolution that is available with fMRI. We utilized a relatively novel method in which fMRI data were collected from children during natural sleep. Stimulus-evoked responses to auditory and visual stimuli as well as stimulus-independent functional networks were examined in typically developing 2-4-year-old children. Reliable fMRI data were collected from 13 children during presentation of auditory stimuli (tones, vocal sounds, and nonvocal sounds) in a block design. Twelve children were presented with visual flashing lights at 2.5 Hz. When analyses combined all three types of auditory stimulus conditions as compared to rest, activation included bilateral superior temporal gyri/sulci (STG/S) and right cerebellum. Direct comparisons between conditions revealed significantly greater responses to nonvocal sounds and tones than to vocal sounds in a number of brain regions including superior temporal gyrus/sulcus, medial frontal cortex and right lateral cerebellum. The response to visual stimuli was localized to occipital cortex. Furthermore, stimulus-independent functional connectivity MRI analyses (fcMRI) revealed functional connectivity between STG and other temporal regions (including contralateral STG) and medial and lateral prefrontal regions. Functional connectivity with an occipital seed was localized to occipital and parietal cortex. In sum, 2-4 year olds showed a differential fMRI response both between stimulus modalities and between stimuli in the auditory modality. Furthermore, superior temporal regions showed functional connectivity with numerous higher-order regions during sleep. We conclude that the use of sleep fMRI may be a valuable tool for examining functional brain organization in young children.

Psychosocial Stress and Brain Function in Adolescent Psychopathology.

PubMed

Quinlan, Erin Burke; Cattrell, Anna; Jia, Tianye; Artiges, Eric; Banaschewski, Tobias; Barker, Gareth; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Brühl, Rüdiger; Conrod, Patricia J; Desrivieres, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Martinot, Jean-Luc; Paillère Martinot, Marie-Laure; Nees, Frauke; Papadopoulos-Orfanos, Dimitri; Paus, Tomáš; Poustka, Luise; Smolka, Michael N; Vetter, Nora C; Walter, Henrik; Whelan, Robert; Glennon, Jeffrey C; Buitelaar, Jan K; Happé, Francesca; Loth, Eva; Barker, Edward D; Schumann, Gunter

2017-08-01

The authors sought to explore how conduct, hyperactivity/inattention, and emotional symptoms are associated with neural reactivity to social-emotional stimuli, and the extent to which psychosocial stress modulates these relationships. Participants were community adolescents recruited as part of the European IMAGEN study. Bilateral amygdala regions of interest were used to assess the relationship between the three symptom domains and functional MRI neural reactivity during passive viewing of dynamic angry and neutral facial expressions. Exploratory functional connectivity and whole brain multiple regression approaches were used to analyze how the symptoms and psychosocial stress relate to other brain regions. In response to the social-emotional stimuli, adolescents with high levels of conduct or hyperactivity/inattention symptoms who had also experienced a greater number of stressful life events showed hyperactivity of the amygdala and several regions across the brain. This effect was not observed with emotional symptoms. A cluster in the midcingulate was found to be common to both conduct problems and hyperactivity symptoms. Exploratory functional connectivity analyses suggested that amygdala-precuneus connectivity is associated with hyperactivity/inattention symptoms. The results link hyperactive amygdala responses and regions critical for top-down emotional processing with high levels of psychosocial stress in individuals with greater conduct and hyperactivity/inattention symptoms. This work highlights the importance of studying how psychosocial stress affects functional brain responses to social-emotional stimuli, particularly in adolescents with externalizing symptoms.

Serotonergic, Brain Volume and Attentional Correlates of Trait Anxiety in Primates

PubMed Central

Mikheenko, Yevheniia; Shiba, Yoshiro; Sawiak, Stephen; Braesicke, Katrin; Cockcroft, Gemma; Clarke, Hannah; Roberts, Angela C

2015-01-01

Trait anxiety is a risk factor for the development and maintenance of affective disorders, and insights into the underlying brain mechanisms are vital for improving treatment and prevention strategies. Translational studies in non-human primates, where targeted neurochemical and genetic manipulations can be made, are critical in view of their close neuroanatomical similarity to humans in brain regions implicated in trait anxiety. Thus, we characterised the serotonergic and regional brain volume correlates of trait-like anxiety in the marmoset monkey. Low- and high-anxious animals were identified by behavioral responses to a human intruder (HI) that are known to be sensitive to anxiolytic drug treatment. Extracellular serotonin levels within the amygdala were measured with in vivo microdialysis, at baseline and in response to challenge with the selective serotonin reuptake inhibitor, citalopram. Regional brain volume was assessed by structural magnetic resonance imaging. Anxious individuals showed persistent, long-term fearful responses to both a HI and a model snake, alongside sustained attention (vigilance) to novel cues in a context associated with unpredictable threat. Neurally, high-anxious marmosets showed reduced amygdala serotonin levels, and smaller volumes in a closely connected prefrontal region, the dorsal anterior cingulate cortex. These findings highlight behavioral and neural similarities between trait-like anxiety in marmosets and humans, and set the stage for further investigation of the processes contributing to vulnerability and resilience to affective disorders. PMID:25586542

Functional specificity for high-level linguistic processing in the human brain.

PubMed

Fedorenko, Evelina; Behr, Michael K; Kanwisher, Nancy

2011-09-27

Neuroscientists have debated for centuries whether some regions of the human brain are selectively engaged in specific high-level mental functions or whether, instead, cognition is implemented in multifunctional brain regions. For the critical case of language, conflicting answers arise from the neuropsychological literature, which features striking dissociations between deficits in linguistic and nonlinguistic abilities, vs. the neuroimaging literature, which has argued for overlap between activations for linguistic and nonlinguistic processes, including arithmetic, domain general abilities like cognitive control, and music. Here, we use functional MRI to define classic language regions functionally in each subject individually and then examine the response of these regions to the nonlinguistic functions most commonly argued to engage these regions: arithmetic, working memory, cognitive control, and music. We find little or no response in language regions to these nonlinguistic functions. These data support a clear distinction between language and other cognitive processes, resolving the prior conflict between the neuropsychological and neuroimaging literatures.

Temporal Profiles Dissociate Regional Extracellular Ethanol versus Dopamine Concentrations

PubMed Central

2015-01-01

In vivo monitoring of dopamine via microdialysis has demonstrated that acute, systemic ethanol increases extracellular dopamine in regions innervated by dopaminergic neurons originating in the ventral tegmental area and substantia nigra. Simultaneous measurement of dialysate dopamine and ethanol allows comparison of the time courses of their extracellular concentrations. Early studies demonstrated dissociations between the time courses of brain ethanol concentrations and dopaminergic responses in the nucleus accumbens (NAc) elicited by acute ethanol administration. Both brain ethanol and extracellular dopamine levels peak during the first 5 min following systemic ethanol administration, but the dopamine response returns to baseline while brain ethanol concentrations remain elevated. Post hoc analyses examined ratios of the dopamine response (represented as a percent above baseline) to tissue concentrations of ethanol at different time points within the first 25–30 min in the prefrontal cortex, NAc core and shell, and dorsomedial striatum following a single intravenous infusion of ethanol (1 g/kg). The temporal patterns of these “response ratios” differed across brain regions, possibly due to regional differences in the mechanisms underlying the decline of the dopamine signal associated with acute intravenous ethanol administration and/or to the differential effects of acute ethanol on the properties of subpopulations of midbrain dopamine neurons. This Review draws on neurochemical, physiological, and molecular studies to summarize the effects of acute ethanol administration on dopamine activity in the prefrontal cortex and striatal regions, to explore the potential reasons for the regional differences observed in the decline of ethanol-induced dopamine signals, and to suggest directions for future research. PMID:25537116

Neural predictors of chocolate intake following chocolate exposure.

PubMed

Frankort, Astrid; Roefs, Anne; Siep, Nicolette; Roebroeck, Alard; Havermans, Remco; Jansen, Anita

2015-04-01

Previous studies have shown that one's brain response to high-calorie food cues can predict long-term weight gain or weight loss. The neural correlates that predict food intake in the short term have, however, hardly been investigated. This study examined which brain regions' activation predicts chocolate intake after participants had been either exposed to real chocolate or to control stimuli during approximately one hour, with interruptions for fMRI measurements. Further we investigated whether the variance in chocolate intake could be better explained by activated brain regions than by self-reported craving. In total, five brain regions correlated with subsequent chocolate intake. The activation of two reward regions (the right caudate and the left frontopolar cortex) correlated positively with intake in the exposure group. The activation of two regions associated with cognitive control (the left dorsolateral and left mid-dorsolateral PFC) correlated negatively with intake in the control group. When the regression analysis was conducted with the exposure and the control group together, an additional region's activation (the right anterior PFC) correlated positively with chocolate intake. In all analyses, the intake variance explained by neural correlates was above and beyond the variance explained by self-reported craving. These results are in line with neuroimaging research showing that brain responses are a better predictor of subsequent intake than self-reported craving. Therefore, our findings might provide for a missing link by associating brain activation, previously shown to predict weight change, with short-term intake. Copyright © 2014 Elsevier Ltd. All rights reserved.

Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains

PubMed Central

Brinkmeyer-Langford, Candice L.; Guan, Jinting; Ji, Guoli; Cai, James J.

2016-01-01

Human aging is associated with cognitive decline and an increased risk of neurodegenerative disease. Our objective for this study was to evaluate potential relationships between age and variation in gene expression across different regions of the brain. We analyzed the Genotype-Tissue Expression (GTEx) data from 54 to 101 tissue samples across 13 brain regions in post-mortem donors of European descent aged between 20 and 70 years at death. After accounting for the effects of covariates and hidden confounding factors, we identified 1446 protein-coding genes whose expression in one or more brain regions is correlated with chronological age at a false discovery rate of 5%. These genes are involved in various biological processes including apoptosis, mRNA splicing, amino acid biosynthesis, and neurotransmitter transport. The distribution of these genes among brain regions is uneven, suggesting variable regional responses to aging. We also found that the aging response of many genes, e.g., TP37 and C1QA, depends on individuals' genotypic backgrounds. Finally, using dispersion-specific analysis, we identified genes such as IL7R, MS4A4E, and TERF1/TERF2 whose expressions are differentially dispersed by aging, i.e., variances differ between age groups. Our results demonstrate that age-related gene expression is brain region-specific, genotype-dependent, and associated with both mean and dispersion changes. Our findings provide a foundation for more sophisticated gene expression modeling in the studies of age-related neurodegenerative diseases. PMID:27536236

Diabetes dietary management alters responses to food pictures in brain regions associated with motivation and emotion: a functional magnetic resonance imaging study.

PubMed

Chechlacz, M; Rotshtein, P; Klamer, S; Porubská, K; Higgs, S; Booth, D; Fritsche, A; Preissl, H; Abele, H; Birbaumer, N; Nouwen, A

2009-03-01

We hypothesised that living with type 2 diabetes would enhance responses to pictures of foods in brain regions known to be involved in learnt food sensory motivation and that these stronger activations would relate to scores for dietary adherence in diabetes and to measures of potential difficulties in adherence. We compared brain responses to food images of 11 people with type 2 diabetes and 12 healthy control participants, matched for age and weight, using functional magnetic resonance imaging (fMRI). Having type 2 diabetes increased responses to pictured foods in the insula, orbitofrontal cortex (OFC) and basal ganglia and, within these regions, the effect of the fat content of the foods was larger in participants with type 2 diabetes than in healthy controls. Furthermore, increased activation to food within the insula and OFC positively correlated with external eating, dietary self-efficacy and dietary self-care. In contrast, responses within subcortical structures (amygdala and basal ganglia) were positively correlated with emotional eating and rated appetite for the food stimuli and negatively correlated with dietary self-care. Type 2 diabetes is associated with changes in brain responses to food that are modulated by dietary self-care. We propose that this is linked to the need to follow a life-long restrictive diet.

Preterm birth and maternal responsiveness during childhood are associated with brain morphology in adolescence.

PubMed

Frye, Richard E; Malmberg, Benjamin; Swank, Paul; Smith, Karen; Landry, Susan

2010-09-01

Although supportive parenting has been shown to have positive effects on development, the neurobiological basis of supportive parenting has not been investigated. Thirty-three adolescents were systemically selected from a longitudinal study on child development based on maternal responsiveness during childhood, a measure of supportive parenting, and whether they were born term or preterm. We analyzed the effect of preterm birth on hemispheric and regional (frontal, temporal, parietal) cortical thickness and surface area using mixed-model analysis while also considering the effect of brain hemisphere (left vs. right). We then determined whether these factors were moderated by maternal responsiveness during childhood. Preterm birth was associated with regional and hemispheric differences in cortical thickness and surface area. Maternal responsiveness during childhood moderated hemispheric cortical thickness. Adolescence with mothers that were inconsistently responsive during childhood demonstrated greater overall cortical thickness and greater asymmetry in cortical thickness during adolescence as compared to adolescence with mothers who were consistently responsive or unresponsive during childhood. Maternal responsiveness and preterm birth did not interact. These data suggest that changes in brain morphology associated with preterm birth continue into adolescence and support the notion that the style of maternal-child interactions during childhood influence brain development into adolescence.

Brain responses differ to faces of mothers and fathers.

PubMed

Arsalidou, Marie; Barbeau, Emmanuel J; Bayless, Sarah J; Taylor, Margot J

2010-10-01

We encounter many faces each day but relatively few are personally familiar. Once faces are familiar, they evoke semantic and social information known about the person. Neuroimaging studies demonstrate differential brain activity to familiar and non-familiar faces; however, brain responses related to personally familiar faces have been more rarely studied. We examined brain activity with fMRI in adults in response to faces of their mothers and fathers compared to faces of celebrities and strangers. Overall, faces of mothers elicited more activity in core and extended brain regions associated with face processing, compared to fathers, celebrity or stranger faces. Fathers' faces elicited activity in the caudate, a deep brain structure associated with feelings of love. These new findings of differential brain responses elicited by faces of mothers and fathers are consistent with psychological research on attachment, evident even during adulthood. 2010 Elsevier Inc. All rights reserved.

Regional TNFα mapping in the brain reveals the striatum as a neuroinflammatory target after ventricular fibrillation cardiac arrest in rats.

PubMed

Janata, Andreas; Magnet, Ingrid A M; Uray, Thomas; Stezoski, Jason P; Janesko-Feldman, Keri; Tisherman, Samuel A; Kochanek, Patrick M; Drabek, Tomas

2014-05-01

Cardiac arrest (CA) triggers neuroinflammation that could play a role in a delayed neuronal death. In our previously established rat model of ventricular fibrillation (VF) CA characterized by extensive neuronal death, we tested the hypothesis that individual brain regions have specific neuroinflammatory responses, as reflected by regional brain tissue levels of tumor necrosis factor (TNF)α and other cytokines. In a prospective study, rats were randomized to 6min (CA6), 8min (CA8) or 10min (CA10) of VF CA, or sham group. Cortex, striatum, hippocampus and cerebellum were evaluated for TNFα and interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12 and interferon gamma at 3h, 6h or 14 d after CA by ELISA and Luminex. Immunohistochemistry was used to determine the cell source of TNFα. CA resulted in a selective TNFα response with significant regional and temporal differences. At 3h after CA, TNFα-levels increased in all regions depending on the duration of the insult. The most pronounced increase was observed in striatum that showed 20-fold increase in CA10 vs. sham, and 3-fold increase vs. CA6 or CA8 group, respectively (p<0.01). TNFα levels in striatum decreased between 3h and 6h, but increased in other regions between 3h and 14 d. TNFα levels remained twofold higher in CA6 vs. shams across brain regions at 14 d (p<0.01). In contrast to pronounced TNFα response, other cytokines showed only a minimal increase in CA6 and CA8 groups vs. sham in all brain regions with the exception that IL-1β increased twofold in cerebellum and striatum (p<0.01). TNFα colocalized with neurons. In conclusion, CA produced a duration-dependent acute TNFα response, with dramatic increase in the striatum where TNFα colocalized with neurons. Increased TNFα levels persist for at least two weeks. This TNFα surge contrasts the lack of an acute increase in other cytokines in brain after CA. Given that striatum is a selectively vulnerable brain region, our data suggest possible role of neuronal TNFα in striatum after CA and identify therapeutic targets for future experiments. This study was approved by the University of Pittsburgh IACUC 1002340A-3. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Insulin sensitivity affects corticolimbic brain responses to visual food cues in polycystic ovary syndrome patients.

PubMed

Alsaadi, Hanin M; Van Vugt, Dean A

2015-11-01

This study examined the effect of insulin sensitivity on the responsiveness of appetite regulatory brain regions to visual food cues. Nineteen participants diagnosed with polycystic ovary syndrome (PCOS) were divided into insulin-sensitive (n=8) and insulin-resistant (n=11) groups based on the homeostatic model assessment of insulin resistance (HOMA2-IR). Subjects underwent functional magnetic resonance imaging (fMRI) while viewing food pictures following water or dextrose consumption. The corticolimbic blood oxygen level dependent (BOLD) responses to high-calorie (HC) or low-calorie (LC) food pictures were compared within and between groups. BOLD responses to food pictures were reduced during a glucose challenge in numerous corticolimbic brain regions in insulin-sensitive but not insulin-resistant subjects. Furthermore, the degree of insulin resistance positively correlated with the corticolimbic BOLD response in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate and ventral tegmental area (VTA) in response to HC pictures, and in the dorsolateral prefrontal cortex (DLPFC), mPFC, anterior cingulate, and insula in response to LC pictures following a glucose challenge. BOLD signal in the OFC, midbrain, hippocampus, and amygdala following a glucose challenge correlated with HOMA2-IR in response to HC-LC pictures. We conclude that the normal inhibition of corticolimbic brain responses to food pictures during a glucose challenge is compromised in insulin-resistant subjects. The increase in brain responsiveness to food pictures during postprandial hyperinsulinemia may lead to greater non-homeostatic eating and perpetuate obesity in insulin-resistant subjects.

Regional rat brain noradrenaline turnover in response to restraint stress.

PubMed

Glavin, G B; Tanaka, M; Tsuda, A; Kohno, Y; Hoaki, Y; Nagasaki, N

1983-08-01

Male Wistar rats were starved for 12 hr and then subjected to either 2 hr of wire mesh "envelope" restraint at room temperature; 2 hr of supine restraint in a specially constructed harness at room temperature or were not restrained. Eight brain regions were examined for NA level and the level of its major metabolite, MHPG-SO4. Plasma corticosterone and gastric ulcer incidence were also measured. All restrained rats displayed marked elevations in MHPG-SO4 levels in most brain regions. In addition, several brain regions in restrained animals showed a reduction in NA level. All restrained rats showed elevated plasma corticosterone levels and evidence of gastric lesions. In general, supine restraint produced greater alterations in regional brain NA turnover, greater evidence of ulcer disease, and higher plasma corticosterone levels than did wire mesh restraint. These data suggest that acute but intense stress in the form of restraint causes markedly altered brain NA activity--a possible neurochemical mechanism underlying the phenomenon of stress-induced disease.

Medication Overuse Headache: Pathophysiological Insights from Structural and Functional Brain MRI Research.

PubMed

Schwedt, Todd J; Chong, Catherine D

2017-07-01

Research imaging of brain structure and function has helped to elucidate the pathophysiology of medication overuse headache (MOH). This is a narrative review of imaging research studies that have investigated brain structural and functional alterations associated with MOH. Studies included in this review have investigated abnormal structure and function of pain processing regions in people with MOH, functional patterns that might predispose individuals to development of MOH, similarity of brain functional patterns in patients with MOH to those found in people with addiction, brain structure that could predict headache improvement following discontinuation of the overused medication, and changes in brain structure and function after discontinuation of medication overuse. MOH is associated with atypical structure and function of brain regions responsible for pain processing as well as brain regions that are commonly implicated in addiction. Several studies have shown "normalization" of structure and function in pain processing regions following discontinuation of the overused medication and resolution of MOH. However, some of the abnormalities in regions also implicated in addiction tend to persist following discontinuation of the overused medication, suggesting that they are a brain trait that predisposes certain individuals to medication overuse and MOH. © 2017 American Headache Society.

Brain activation and connectivity of social cognition using diffuse optical imaging

NASA Astrophysics Data System (ADS)

Zhu, Banghe; Godavarty, Anuradha

2009-02-01

In the current research, diffuse optical imaging (DOI) is used for the first time towards studies related to sociocommunication impairments, which is a characteristic feature of autism. DOI studies were performed on normal adult volunteers to determine the differences in the brain activation (cognitive regions) in terms of the changes in the cerebral blood oxygenation levels in response to joint and non-joint attention based stimulus (i.e. socio-communicative paradigms shown as video clips). Functional connectivity models are employed to assess the extent of synchronization between the left and right pre-frontal regions of the brain in response to the above stimuli.

Brain reward region responsivity of adolescents with and without parental substance use disorders.

PubMed

Stice, Eric; Yokum, Sonja

2014-09-01

The present study tested the competing hypotheses that adolescents at risk for future substance abuse and dependence by virtue of parental substance use disorders show either weaker or stronger responsivity of brain regions implicated in reward relative to youth without parental history of substance use disorders. Adolescents (n = 52) matched on demographics with and without parental substance use disorders, as determined by diagnostic interviews, who denied substance use in the past year were compared on functional MRI (fMRI) paradigms assessing neural response to receipt and anticipated receipt of monetary and food reward. Parental-history-positive versus -negative adolescents showed greater activation in the left dorsolateral prefrontal cortex and bilateral putamen, and less activation in the fusiform gyrus and inferior temporal gyrus in response to anticipating winning money, as well as greater activation in the left midbrain and right paracentral lobule, and less activation in the right middle frontal gyrus in response to milkshake receipt. Results indicate that adolescents at risk for future onset of substance use disorders show elevated responsivity of brain regions implicated in reward, extending results from 2 smaller prior studies that found that individuals with versus without parental alcohol use disorders showed greater reward region response to anticipated monetary reward and pictures of alcohol. Collectively, results provide support for the reward surfeit model of substance use disorders, rather than the reward deficit model.

Neural correlates of stress- and food cue-induced food craving in obesity: association with insulin levels.

PubMed

Jastreboff, Ania M; Sinha, Rajita; Lacadie, Cheryl; Small, Dana M; Sherwin, Robert S; Potenza, Marc N

2013-02-01

Obesity is associated with alterations in corticolimbic-striatal brain regions involved in food motivation and reward. Stress and the presence of food cues may each motivate eating and engage corticolimibic-striatal neurocircuitry. It is unknown how these factors interact to influence brain responses and whether these interactions are influenced by obesity, insulin levels, and insulin sensitivity. We hypothesized that obese individuals would show greater responses in corticolimbic-striatal neurocircuitry after exposure to stress and food cues and that brain activations would correlate with subjective food craving, insulin levels, and HOMA-IR. Fasting insulin levels were assessed in obese and lean subjects who were exposed to individualized stress and favorite-food cues during functional MRI. Obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food and stress cues. In obese but not lean individuals, food craving, insulin, and HOMA-IR levels correlated positively with neural activity in corticolimbic-striatal brain regions during favorite-food and stress cues. The relationship between insulin resistance and food craving in obese individuals was mediated by activity in motivation-reward regions including the striatum, insula, and thalamus. These findings demonstrate that obese, but not lean, individuals exhibit increased corticolimbic-striatal activation in response to favorite-food and stress cues and that these brain responses mediate the relationship between HOMA-IR and food craving. Improving insulin sensitivity and in turn reducing corticolimbic-striatal reactivity to food cues and stress may diminish food craving and affect eating behavior in obesity.

Neural Correlates of Stress- and Food Cue–Induced Food Craving in Obesity

PubMed Central

Jastreboff, Ania M.; Sinha, Rajita; Lacadie, Cheryl; Small, Dana M.; Sherwin, Robert S.; Potenza, Marc N.

2013-01-01

OBJECTIVE Obesity is associated with alterations in corticolimbic-striatal brain regions involved in food motivation and reward. Stress and the presence of food cues may each motivate eating and engage corticolimibic-striatal neurocircuitry. It is unknown how these factors interact to influence brain responses and whether these interactions are influenced by obesity, insulin levels, and insulin sensitivity. We hypothesized that obese individuals would show greater responses in corticolimbic-striatal neurocircuitry after exposure to stress and food cues and that brain activations would correlate with subjective food craving, insulin levels, and HOMA-IR. RESEARCH DESIGN AND METHODS Fasting insulin levels were assessed in obese and lean subjects who were exposed to individualized stress and favorite-food cues during functional MRI. RESULTS Obese, but not lean, individuals exhibited increased activation in striatal, insular, and hypothalamic regions during exposure to favorite-food and stress cues. In obese but not lean individuals, food craving, insulin, and HOMA-IR levels correlated positively with neural activity in corticolimbic-striatal brain regions during favorite-food and stress cues. The relationship between insulin resistance and food craving in obese individuals was mediated by activity in motivation-reward regions including the striatum, insula, and thalamus. CONCLUSIONS These findings demonstrate that obese, but not lean, individuals exhibit increased corticolimbic-striatal activation in response to favorite-food and stress cues and that these brain responses mediate the relationship between HOMA-IR and food craving. Improving insulin sensitivity and in turn reducing corticolimbic-striatal reactivity to food cues and stress may diminish food craving and affect eating behavior in obesity. PMID:23069840

Brain regions involved in the development of acute phase responses accompanying fever in rabbits.

PubMed Central

Morimoto, A; Murakami, N; Nakamori, T; Sakata, Y; Watanabe, T

1989-01-01

1. The effects of microinjection of rabbit endogenous pyrogen and human recombinant interleukin-1 alpha on rectal temperature and acute phase responses were extensively examined in forty different brain regions of rabbits. The acute phase responses that were investigated were the changes in plasma levels of iron, zinc and copper concentration and the changes in circulating leucocyte count. 2. The rostral hypothalamic regions, such as nucleus broca ventralis, preoptic area and anterior hypothalamic region, responded to the microinjection of endogenous pyrogen or interleukin-1 by producing both fever and acute phase responses. 3. The microinjection of endogenous pyrogen or interleukin-1 into the rostral hypothalamic regions significantly decreased the plasma levels of iron and zinc concentration 8 and 24 h after injection. The circulating leucocyte count increased 8 h after injection. However, neither the injections of endogenous pyrogen nor interleukin-1 affected the number of red blood cells. 4. The present results show that the rostral hypothalamic regions respond directly to endogenous pyrogen or interleukin-1 with the consequent development of fever and acute phase responses. PMID:2514261

Simultaneous recording of fluorescence and electrical signals by photometric patch electrode in deep brain regions in vivo

PubMed Central

Hirai, Yasuharu; Nishino, Eri

2015-01-01

Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices. PMID:25761950

Simultaneous recording of fluorescence and electrical signals by photometric patch electrode in deep brain regions in vivo.

PubMed

Hirai, Yasuharu; Nishino, Eri; Ohmori, Harunori

2015-06-01

Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices. Copyright © 2015 the American Physiological Society.

Naproxen effects on brain response to painful pressure stimulation in patients with knee osteoarthritis: a double-blind, randomized, placebo-controlled, single-dose study.

PubMed

Giménez, Mónica; Pujol, Jesús; Ali, Zahid; López-Solà, Marina; Contreras-Rodríguez, Oren; Deus, Joan; Ortiz, Héctor; Soriano-Mas, Carles; Llorente-Onaindia, Jone; Monfort, Jordi

2014-11-01

The aim of our study was to investigate the effects of naproxen, an antiinflammatory analgesic drug, on brain response to painful stimulation on the affected knee in chronic osteoarthritis (OA) using functional magnetic resonance imaging (fMRI) in a double-blind, placebo-controlled study. A sample of 25 patients with knee OA received naproxen (500 mg), placebo, or no treatment in 3 separate sessions in a randomized manner. Pressure stimulation was applied to the medial articular interline of the knee during the fMRI pain sequence. We evaluated subjective pain ratings at every session and their association with brain responses to pain. An fMRI control paradigm was included to discard global brain vascular effects of naproxen. We found brain activation reductions under naproxen compared to no treatment in different cortical and subcortical core pain processing regions (p≤0.001). Compared to placebo, naproxen triggered an attenuation of amygdala activation (p=0.001). Placebo extended its attenuation effects beyond the classical pain processing network (p≤0.001). Subjective pain scores during the fMRI painful task differed between naproxen and no treatment (p=0.037). Activation attenuation under naproxen in different regions (i.e., ventral brain, cingulate gyrus) was accompanied by an improvement in the subjective pain complaints (p≤0.002). Naproxen effectively reduces pain-related brain responses involving different regions and the attenuation is related to subjective pain changes. Our current work yields further support to the utility of fMRI to objectify the acute analgesic effects of a single naproxen dose in patients affected by knee OA. The trial was registered at the EuropeanClinicalTrials Database, "EudraCT Number 2008-004501-33".

Cross-Species Affective Neuroscience Decoding of the Primal Affective Experiences of Humans and Related Animals

PubMed Central

Panksepp, Jaak

2011-01-01

Background The issue of whether other animals have internally felt experiences has vexed animal behavioral science since its inception. Although most investigators remain agnostic on such contentious issues, there is now abundant experimental evidence indicating that all mammals have negatively and positively-valenced emotional networks concentrated in homologous brain regions that mediate affective experiences when animals are emotionally aroused. That is what the neuroscientific evidence indicates. Principal Findings The relevant lines of evidence are as follows: 1) It is easy to elicit powerful unconditioned emotional responses using localized electrical stimulation of the brain (ESB); these effects are concentrated in ancient subcortical brain regions. Seven types of emotional arousals have been described; using a special capitalized nomenclature for such primary process emotional systems, they are SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF and PLAY. 2) These brain circuits are situated in homologous subcortical brain regions in all vertebrates tested. Thus, if one activates FEAR arousal circuits in rats, cats or primates, all exhibit similar fear responses. 3) All primary-process emotional-instinctual urges, even ones as complex as social PLAY, remain intact after radical neo-decortication early in life; thus, the neocortex is not essential for the generation of primary-process emotionality. 4) Using diverse measures, one can demonstrate that animals like and dislike ESB of brain regions that evoke unconditioned instinctual emotional behaviors: Such ESBs can serve as ‘rewards’ and ‘punishments’ in diverse approach and escape/avoidance learning tasks. 5) Comparable ESB of human brains yield comparable affective experiences. Thus, robust evidence indicates that raw primary-process (i.e., instinctual, unconditioned) emotional behaviors and feelings emanate from homologous brain functions in all mammals (see Appendix S1), which are regulated by higher brain regions. Such findings suggest nested-hierarchies of BrainMind affective processing, with primal emotional functions being foundational for secondary-process learning and memory mechanisms, which interface with tertiary-process cognitive-thoughtful functions of the BrainMind. PMID:21915252

Cross-species affective neuroscience decoding of the primal affective experiences of humans and related animals.

PubMed

Panksepp, Jaak

2011-01-01

The issue of whether other animals have internally felt experiences has vexed animal behavioral science since its inception. Although most investigators remain agnostic on such contentious issues, there is now abundant experimental evidence indicating that all mammals have negatively and positively-valenced emotional networks concentrated in homologous brain regions that mediate affective experiences when animals are emotionally aroused. That is what the neuroscientific evidence indicates. The relevant lines of evidence are as follows: 1) It is easy to elicit powerful unconditioned emotional responses using localized electrical stimulation of the brain (ESB); these effects are concentrated in ancient subcortical brain regions. Seven types of emotional arousals have been described; using a special capitalized nomenclature for such primary process emotional systems, they are SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF and PLAY. 2) These brain circuits are situated in homologous subcortical brain regions in all vertebrates tested. Thus, if one activates FEAR arousal circuits in rats, cats or primates, all exhibit similar fear responses. 3) All primary-process emotional-instinctual urges, even ones as complex as social PLAY, remain intact after radical neo-decortication early in life; thus, the neocortex is not essential for the generation of primary-process emotionality. 4) Using diverse measures, one can demonstrate that animals like and dislike ESB of brain regions that evoke unconditioned instinctual emotional behaviors: Such ESBs can serve as 'rewards' and 'punishments' in diverse approach and escape/avoidance learning tasks. 5) Comparable ESB of human brains yield comparable affective experiences. Thus, robust evidence indicates that raw primary-process (i.e., instinctual, unconditioned) emotional behaviors and feelings emanate from homologous brain functions in all mammals (see Appendix S1), which are regulated by higher brain regions. Such findings suggest nested-hierarchies of BrainMind affective processing, with primal emotional functions being foundational for secondary-process learning and memory mechanisms, which interface with tertiary-process cognitive-thoughtful functions of the BrainMind.

Acute pharmacologically induced shifts in serotonin availability abolish emotion-selective responses to negative face emotions in distinct brain networks.

PubMed

Grady, Cheryl L; Siebner, Hartwig R; Hornboll, Bettina; Macoveanu, Julian; Paulson, Olaf B; Knudsen, Gitte M

2013-05-01

Pharmacological manipulation of serotonin availability can alter the processing of facial expressions of emotion. Using a within-subject design, we measured the effect of serotonin on the brain's response to aversive face emotions with functional MRI while 20 participants judged the gender of neutral, fearful and angry faces. In three separate and counterbalanced sessions, participants received citalopram (CIT) to raise serotonin levels, underwent acute tryptophan depletion (ATD) to lower serotonin, or were studied without pharmacological challenge (Control). An analysis designed to identify distributed brain responses identified two brain networks with modulations of activity related to face emotion and serotonin level. The first network included the left amygdala, bilateral striatum, and fusiform gyri. During the Control session this network responded only to fearful faces; increasing serotonin decreased this response to fear, whereas reducing serotonin enhanced the response of this network to angry faces. The second network involved bilateral amygdala and ventrolateral prefrontal cortex, and these regions also showed increased activity to fear during the Control session. Both drug challenges enhanced the neural response of this set of regions to angry faces, relative to Control, and CIT also enhanced activity for neutral faces. The net effect of these changes in both networks was to abolish the selective response to fearful expressions. These results suggest that a normal level of serotonin is critical for maintaining a differentiated brain response to threatening face emotions. Lower serotonin leads to a broadening of a normally fear-specific response to anger, and higher levels reduce the differentiated brain response to aversive face emotions. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

The craving stops before you feel it: neural correlates of chocolate craving during cue exposure with response prevention.

PubMed

Frankort, Astrid; Roefs, Anne; Siep, Nicolette; Roebroeck, Alard; Havermans, Remco; Jansen, Anita

2014-06-01

Cue reactivity and craving can be influenced by cue exposure with response prevention (CERP). This study investigated the neural correlates of CERP using functional magnetic resonance imaging, while participants smelled chocolate (17 participants) or a control object (17 participants). CERP was interrupted by 7 scanning sequences measuring the brain response to neutral and chocolate pictures. Chocolate craving was hypothesized to be mirrored by activation in brain reward regions. As expected, control group craving remained similar throughout the session. A short exposure (30 min) increased chocolate craving in the experimental group, which was mirrored by significant group differences in activation in brain reward regions. Unexpectedly, a long exposure (60 min) did not lead to craving extinction in the experimental group, although craving started to decrease at this point. On a neural level, however, activation in regions of interest in the experimental group seemed to have extinguished after the long exposure, as activation levels returned to or fell below control group levels. These results indicate that brain reward activation during CERP is linked to craving, at least for a short exposure. Regarding a longer exposure, the decline in brain reward activation in the experimental group may be a precursor of a decrease in craving.

Neuroblast Distribution after Cortical Impact Is Influenced by White Matter Injury in the Immature Gyrencephalic Brain

PubMed Central

Taylor, Sabrina R.; Smith, Colin M.; Keeley, Kristen L.; McGuone, Declan; Dodge, Carter P.; Duhaime, Ann-Christine; Costine, Beth A.

2016-01-01

Cortical contusions are a common type of traumatic brain injury (TBI) in children. Current knowledge of neuroblast response to cortical injury arises primarily from studies utilizing aspiration or cryoinjury in rodents. In infants and children, cortical impact affects both gray and white matter and any neurogenic response may be complicated by the large expanse of white matter between the subventricular zone (SVZ) and the cortex, and the large number of neuroblasts in transit along the major white matter tracts to populate brain regions. Previously, we described an age-dependent increase of neuroblasts in the SVZ in response to cortical impact in the immature gyrencephalic brain. Here, we investigate if neuroblasts target the injury, if white matter injury influences repair efforts, and if postnatal population of brain regions are disrupted. Piglets received a cortical impact to the rostral gyrus cortex or sham surgery at postnatal day (PND) 7, BrdU 2 days prior to (PND 5 and 6) or after injury (PND 7 and 8), and brains were collected at PND 14. Injury did not alter the number of neuroblasts in the white matter between the SVZ and the rostral gyrus. In the gray matter of the injury site, neuroblast density was increased in cavitated lesions, and the number of BrdU+ neuroblasts was increased, but comprised less than 1% of all neuroblasts. In the white matter of the injury site, neuroblasts with differentiating morphology were densely arranged along the cavity edge. In a ventral migratory stream, neuroblast density was greater in subjects with a cavitated lesion, indicating that TBI may alter postnatal development of regions supplied by that stream. Cortical impact in the immature gyrencephalic brain produced complicated and variable lesions, increased neuroblast density in cavitated gray matter, resulted in potentially differentiating neuroblasts in the white matter, and may alter the postnatal population of brain regions utilizing a population of neuroblasts that were born prior to PND 5. This platform may be useful to continue to study potential complications of white matter injury and alterations of postnatal population of brain regions, which may contribute to the chronic effects of TBI in children. PMID:27601978

Nonlinear response of the anterior cingulate and prefrontal cortex in schizophrenia as a function of variable attentional control.

PubMed

Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Caforio, Grazia; Romano, Raffaella; Lobianco, Luciana; Fazio, Leonardo; Di Giorgio, Annabella; Latorre, Valeria; Sambataro, Fabio; Popolizio, Teresa; Nardini, Marcello; Mattay, Venkata S; Weinberger, Daniel R; Bertolino, Alessandro

2010-04-01

Previous studies have reported abnormal prefrontal and cingulate activity during attentional control processing in schizophrenia. However, it is not clear how variation in attentional control load modulates activity within these brain regions in this brain disorder. The aim of this study in schizophrenia is to investigate the impact of increasing levels of attentional control processing on prefrontal and cingulate activity. Blood oxygen level-dependent (BOLD) responses of 16 outpatients with schizophrenia were compared with those of 21 healthy subjects while performing a task eliciting increasing levels of attentional control during event-related functional magnetic resonance imaging at 3 T. Results showed reduced behavioral performance in patients at greater attentional control levels. Imaging data indicated greater prefrontal activity at intermediate attentional control levels in patients but greater prefrontal and cingulate responses at high attentional control demands in controls. The BOLD activity profile of these regions in controls increased linearly with increasing cognitive loads, whereas in patients, it was nonlinear. Correlation analysis consistently showed differential region and load-specific relationships between brain activity and behavior in the 2 groups. These results indicate that varying attentional control load is associated in schizophrenia with load- and region-specific modification of the relationship between behavior and brain activity, possibly suggesting earlier saturation of cognitive capacity.

Cocaine-Induced Structural Plasticity in Input Regions to Distinct Cell Types in Nucleus Accumbens.

PubMed

Barrientos, Cindy; Knowland, Daniel; Wu, Mingche M J; Lilascharoen, Varoth; Huang, Kee Wui; Malenka, Robert C; Lim, Byung Kook

2018-05-09

The nucleus accumbens (NAc) is a brain region implicated in pathological motivated behaviors such as drug addiction and is composed predominantly of two discrete populations of neurons, dopamine receptor-1- and dopamine receptor-2-expressing medium spiny neurons (D1-MSNs and D2-MSNs, respectively). It is unclear whether these populations receive inputs from different brain areas and whether input regions to these cell types undergo distinct structural adaptations in response to the administration of addictive drugs such as cocaine. Using a modified rabies virus-mediated tracing method, we created a comprehensive brain-wide monosynaptic input map to NAc D1- and D2-MSNs. Next, we analyzed nearly 2000 dendrites and 125,000 spines of neurons across four input regions (the prelimbic cortex, medial orbitofrontal cortex, basolateral amygdala, and ventral hippocampus) at four separate time points during cocaine administration and withdrawal to examine changes in spine density in response to repeated intraperitoneal cocaine injection in mice. D1- and D2-MSNs display overall similar input profiles, with the exception that D1-MSNs receive significantly more input from the medial orbitofrontal cortex. We found that neurons in distinct brain areas projecting to D1- and D2-MSNs display different adaptations in dendritic spine density at different stages of cocaine administration and withdrawal. While NAc D1- and D2-MSNs receive input from similar brain structures, cocaine-induced spine density changes in input regions are quite distinct and dynamic. While previous studies have focused on input-specific postsynaptic changes within NAc MSNs in response to cocaine, these findings emphasize the dramatic changes that occur in the afferent input regions as well. Published by Elsevier Inc.

Transcranial focused ultrasound stimulation of human primary visual cortex

NASA Astrophysics Data System (ADS)

Lee, Wonhye; Kim, Hyun-Chul; Jung, Yujin; Chung, Yong An; Song, In-Uk; Lee, Jong-Hwan; Yoo, Seung-Schik

2016-09-01

Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.

Decreased functional brain activation in Friedreich ataxia using the Simon effect task.

PubMed

Georgiou-Karistianis, N; Akhlaghi, H; Corben, L A; Delatycki, M B; Storey, E; Bradshaw, J L; Egan, G F

2012-08-01

The present study applied the Simon effect task to examine the pattern of functional brain reorganization in individuals with Friedreich ataxia (FRDA), using functional magnetic resonance imaging (fMRI). Thirteen individuals with FRDA and 14 age and sex matched controls participated, and were required to respond to either congruent or incongruent arrow stimuli, presented either to the left or right of a screen, via laterally-located button press responses. Although the Simon effect (incongruent minus congruent stimuli) showed common regions of activation in both groups, including the superior and middle prefrontal cortices, insulae, superior and inferior parietal lobules (LPs, LPi), occipital cortex and cerebellum, there was reduced functional activation across a range of brain regions (cortical, subcortical and cerebellar) in individuals with FRDA. The greater Simon effect behaviourally in individuals with FRDA, compared with controls, together with concomitant reductions in functional brain activation and reduced functional connectivity between cortical and sub-cortical regions, implies a likely disruption of cortico-cerebellar loops and ineffective engagement of cognitive/attention regions required for response suppression. Copyright © 2012 Elsevier Inc. All rights reserved.

Divergent and nonuniform gene expression patterns in mouse brain

PubMed Central

Morris, John A.; Royall, Joshua J.; Bertagnolli, Darren; Boe, Andrew F.; Burnell, Josh J.; Byrnes, Emi J.; Copeland, Cathy; Desta, Tsega; Fischer, Shanna R.; Goldy, Jeff; Glattfelder, Katie J.; Kidney, Jolene M.; Lemon, Tracy; Orta, Geralyn J.; Parry, Sheana E.; Pathak, Sayan D.; Pearson, Owen C.; Reding, Melissa; Shapouri, Sheila; Smith, Kimberly A.; Soden, Chad; Solan, Beth M.; Weller, John; Takahashi, Joseph S.; Overly, Caroline C.; Lein, Ed S.; Hawrylycz, Michael J.; Hohmann, John G.; Jones, Allan R.

2010-01-01

Considerable progress has been made in understanding variations in gene sequence and expression level associated with phenotype, yet how genetic diversity translates into complex phenotypic differences remains poorly understood. Here, we examine the relationship between genetic background and spatial patterns of gene expression across seven strains of mice, providing the most extensive cellular-resolution comparative analysis of gene expression in the mammalian brain to date. Using comprehensive brainwide anatomic coverage (more than 200 brain regions), we applied in situ hybridization to analyze the spatial expression patterns of 49 genes encoding well-known pharmaceutical drug targets. Remarkably, over 50% of the genes examined showed interstrain expression variation. In addition, the variability was nonuniformly distributed across strain and neuroanatomic region, suggesting certain organizing principles. First, the degree of expression variance among strains mirrors genealogic relationships. Second, expression pattern differences were concentrated in higher-order brain regions such as the cortex and hippocampus. Divergence in gene expression patterns across the brain could contribute significantly to variations in behavior and responses to neuroactive drugs in laboratory mouse strains and may help to explain individual differences in human responsiveness to neuroactive drugs. PMID:20956311

Prediction of human errors by maladaptive changes in event-related brain networks.

PubMed

Eichele, Tom; Debener, Stefan; Calhoun, Vince D; Specht, Karsten; Engel, Andreas K; Hugdahl, Kenneth; von Cramon, D Yves; Ullsperger, Markus

2008-04-22

Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional MRI and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve approximately 30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations.

Prediction of human errors by maladaptive changes in event-related brain networks

PubMed Central

Eichele, Tom; Debener, Stefan; Calhoun, Vince D.; Specht, Karsten; Engel, Andreas K.; Hugdahl, Kenneth; von Cramon, D. Yves; Ullsperger, Markus

2008-01-01

Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional MRI and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve ≈30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations. PMID:18427123

Are age and sex differences in brain oxytocin receptors related to maternal and infanticidal behavior in naïve mice?

PubMed

Olazábal, Daniel E; Alsina-Llanes, Marcela

2016-01-01

This article is part of a Special Issue "Parental Care". There is significant variability in the behavioral responses displayed by naïve young and adult mice when first exposed to pups. This variability has been associated with differences in the expression of oxytocin receptors (OXTRs) in the brain in several species. Experiment I investigated the behavioral responses of juvenile, adolescent, and adult CB57BL/6 males and females when first exposed to pups. We found an age increase in maternal females (11% of juveniles, 20% of adolescents, and 50% of young adults), and infanticidal males (0% of juveniles, 30% of adolescents, 44.5% of young adults, and 100% of older adults). Experiment II investigated OXTR density in the brain of juvenile and adult mice. Our results revealed an age decline in the density of OXTR in several brain regions, including the lateral septum, cingulated and posterior paraventricular thalamic nucleus in both males and females. Adult females had higher OXTR density in the ventromedial nucleus/postero-ventral hypothalamus (VMH) and the accessory olfactory bulb (AOB), but lower density in the ventral region of the lateral septum (LSv) than juveniles. Males had lower OXTR density in the anterior olfactory area (AOA) compared to juveniles. No age or sex differences were found in the medial preoptic area, and amygdaloid nuclei, among other brain regions. This study suggests that 1) maturation of parental and infanticidal behavioral responses is not reached until adulthood; 2) the pattern of development of OXTR in the mouse brain is unique, region specific, and differs from that observed in other rodents; 3) either up or down regulation of OXTR in a few brain regions (VMH/AOB/LSv/AOA) might contribute to age or sex differences in parental or infanticidal behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Structural and Functional Correlates of Visual Field Asymmetry in the Human Brain by Diffusion Kurtosis MRI and Functional MRI

PubMed Central

O’Connell, Caitlin; Ho, Leon C.; Murphy, Matthew C.; Conner, Ian P.; Wollstein, Gadi; Cham, Rakie; Chan, Kevin C.

2016-01-01

Human visual performance has been observed to exhibit superiority in localized regions of the visual field across many classes of stimuli. However, the underlying neural mechanisms remain unclear. This study aims to determine if the visual information processing in the human brain is dependent on the location of stimuli in the visual field and the corresponding neuroarchitecture using blood-oxygenation-level-dependent functional MRI (fMRI) and diffusion kurtosis MRI (DKI), respectively in 15 healthy individuals at 3 Tesla. In fMRI, visual stimulation to the lower hemifield showed stronger brain responses and larger brain activation volumes than the upper hemifield, indicative of the differential sensitivity of the human brain across the visual field. In DKI, the brain regions mapping to the lower visual field exhibited higher mean kurtosis but not fractional anisotropy or mean diffusivity when compared to the upper visual field. These results suggested the different distributions of microstructural organization across visual field brain representations. There was also a strong positive relationship between diffusion kurtosis and fMRI responses in the lower field brain representations. In summary, this study suggested the structural and functional brain involvements in the asymmetry of visual field responses in humans, and is important to the neurophysiological and psychological understanding of human visual information processing. PMID:27631541

Cocaine-associated odor cue re-exposure increases blood oxygenation level dependent signal in memory and reward regions of the maternal rat brain.

PubMed

Caffrey, Martha K; Febo, Marcelo

2014-01-01

Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and -Cue). The BOLD response to +Cue and -Cue was measured in dams on postpartum days 2-4. Odor cues were delivered to dams in the absence and then the presence of pups. Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus -Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

COCAINE-ASSOCIATED ODOR CUE RE-EXPOSURE INCREASES BLOOD OXYGENATION LEVEL DEPENDENT SIGNAL IN MEMORY AND REWARD REGIONS OF THE MATERNAL RAT BRAIN*

PubMed Central

Caffrey, Martha K.; Febo, Marcelo

2013-01-01

BACKGROUND Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue. METHODS Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and −Cue). The BOLD response to +Cue and −Cue was measured in dams on postpartum days 2–4. Odor cues were delivered to dams in the absence and then the presence of pups. RESULTS Our data indicate that several limbic and cognitive regions of the maternal rat brain show a greater BOLD signal response to a +Cue versus −Cue. These include dorsal striatum, prelimbic cortex, parietal cortex, habenula, bed nucleus of stria terminalis, lateral septum and the mediodorsal and the anterior thalamic nucleus. Of the aforementioned brain regions, only the parietal cortex of cocaine treated dams showed a significant modulatory effect of pup presence. In this area of the cortex, cocaine exposed maternal rats showed a greater BOLD activation in response to the +Cue in the presence than in the absence of pups. CONCLUSIONS Specific regions of the cocaine exposed maternal rat brain are strongly reactive to drug associated cues. The regions implicated in cue reactivity have been previously reported in clinical imaging work, and previous work supports their role in various motivational and cognitive functions. PMID:24183499

Neuroimaging in Posttraumatic Stress Disorder and Other Stress-related Disorders

PubMed Central

Bremner, J. Douglas

2009-01-01

Synopsis Traumatic stress has a broad range of effects on the brain. Brain areas implicated in the stress response include the amygdala, hippocampus, and prefrontal cortex. Studies in patients with posttraumatic stress disorder (PTSD) and other psychiatric disorders related to stress have replicated findings in animal studies by finding alterations in these brain areas. Brain regions implicated in PTSD also play an important role in memory function, highlighting the important interplay between memory and the traumatic stress response. Abnormalities in these brain areas are hypothesized to underlie symptoms of PTSD and other stress-related psychiatric disorders. PMID:17983968

Brain systems for visual perspective taking and action perception.

PubMed

Mazzarella, Elisabetta; Ramsey, Richard; Conson, Massimiliano; Hamilton, Antonia

2013-01-01

Taking another person's viewpoint and making sense of their actions are key processes that guide social behavior. Previous neuroimaging investigations have largely studied these processes separately. The current study used functional magnetic resonance imaging to examine how the brain incorporates another person's viewpoint and actions into visual perspective judgments. Participants made a left-right judgment about the location of a target object from their own (egocentric) or an actor's visual perspective (altercentric). Actor location varied around a table and the actor was either reaching or not reaching for the target object. Analyses examined brain regions engaged in the egocentric and altercentric tasks, brain regions where response magnitude tracked the orientation of the actor in the scene and brain regions sensitive to the action performed by the actor. The blood oxygen level-dependent (BOLD) response in dorsomedial prefrontal cortex (dmPFC) was sensitive to actor orientation in the altercentric task, whereas the response in right inferior frontal gyrus (IFG) was sensitive to actor orientation in the egocentric task. Thus, dmPFC and right IFG may play distinct but complementary roles in visual perspective taking (VPT). Observation of a reaching actor compared to a non-reaching actor yielded activation in lateral occipitotemporal cortex, regardless of task, showing that these regions are sensitive to body posture independent of social context. By considering how an observed actor's location and action influence the neural bases of visual perspective judgments, the current study supports the view that multiple neurocognitive "routes" operate during VPT.

Neurocognitive Brain Response to Transient Impairment of Wernicke's Area

PubMed Central

Mason, Robert A.; Prat, Chantel S.; Just, Marcel Adam

2014-01-01

This study examined how the brain system adapts and reconfigures its information processing capabilities to maintain cognitive performance after a key cortical center [left posterior superior temporal gyrus (LSTGp)] is temporarily impaired during the performance of a language comprehension task. By applying repetitive transcranial magnetic stimulation (rTMS) to LSTGp and concurrently assessing the brain response with functional magnetic resonance imaging, we found that adaptation consisted of 1) increased synchronization between compensating regions coupled with a decrease in synchronization within the primary language network and 2) a decrease in activation at the rTMS site as well as in distal regions, followed by their recovery. The compensatory synchronization included 3 centers: The contralateral homolog (RSTGp) of the area receiving rTMS, areas adjacent to the rTMS site, and a region involved in discourse monitoring (medial frontal gyrus). This approach reveals some principles of network-level adaptation to trauma with potential application to traumatic brain injury, stroke, and seizure. PMID:23322403

Neurocognitive brain response to transient impairment of Wernicke's area.

PubMed

Mason, Robert A; Prat, Chantel S; Just, Marcel Adam

2014-06-01

This study examined how the brain system adapts and reconfigures its information processing capabilities to maintain cognitive performance after a key cortical center [left posterior superior temporal gyrus (LSTGp)] is temporarily impaired during the performance of a language comprehension task. By applying repetitive transcranial magnetic stimulation (rTMS) to LSTGp and concurrently assessing the brain response with functional magnetic resonance imaging, we found that adaptation consisted of 1) increased synchronization between compensating regions coupled with a decrease in synchronization within the primary language network and 2) a decrease in activation at the rTMS site as well as in distal regions, followed by their recovery. The compensatory synchronization included 3 centers: The contralateral homolog (RSTGp) of the area receiving rTMS, areas adjacent to the rTMS site, and a region involved in discourse monitoring (medial frontal gyrus). This approach reveals some principles of network-level adaptation to trauma with potential application to traumatic brain injury, stroke, and seizure.

Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

PubMed

Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

2014-07-01

The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

DAT Genotype Modulates Brain and Behavioral Responses Elicited by Cigarette Cues

PubMed Central

Franklin, Teresa R; Lohoff, Falk W; Wang, Ze; Sciortino, Nathan; Harper, Derek; Li, Yin; Jens, Will; Cruz, Jeffrey; Kampman, Kyle; Ehrman, Ron; Berrettini, Wade; Detre, John A; O'Brien, Charles P; Childress, Anna Rose

2011-01-01

We previously demonstrated differential activation of the mesocorticolimbic reward circuitry in response to cigarette cues independent of withdrawal. Despite robust effects, we noted considerable individual variability in brain and subjective responses. As dopamine (DA) is critical for reward and its predictive signals, genetically driven variation in DA transmission may account for the observed differences. Evidence suggests that a variable number of tandem repeats (VNTRs) polymorphism in the DA transporter (DAT) SLC6A3 gene may influence DA transport. Brain and behavioral responses may be enhanced in probands carrying the 9-repeat allele. To test this hypothesis, perfusion fMR images were acquired during cue exposure in 19 smokers genotyped for the 40 bp VNTR polymorphism in the SLC6A3 gene. Contrasts between groups revealed that 9-repeat (9-repeats) had a greater response to smoking (vs nonsmoking) cues than smokers homozygous for the 10-repeat allele (10/10-repeats) bilaterally in the interconnected ventral striatal/pallidal/orbitofrontal cortex regions (VS/VP/OFC). Activity was increased in 9-repeats and decreased in 10/10-repeats in the VS/VP/OFC (p<0.001 for all analyses). Brain activity and craving was strongly correlated in 10/10-repeats in these regions and others (anterior cingulate, parahippocampal gyrus, and insula; r2 = 0.79–0.86, p<0.001 in all regions). Alternatively, there were no significant correlations between brain and behavior in 9-repeats. There were no differences in cigarette dependence, demographics, or resting baseline neural activity between groups. These results provide evidence that genetic variation in the DAT gene contributes to the neural and behavioral responses elicited by smoking cues. PMID:18704100

The highly sensitive brain: an fMRI study of sensory processing sensitivity and response to others' emotions.

PubMed

Acevedo, Bianca P; Aron, Elaine N; Aron, Arthur; Sangster, Matthew-Donald; Collins, Nancy; Brown, Lucy L

2014-07-01

Theory and research suggest that sensory processing sensitivity (SPS), found in roughly 20% of humans and over 100 other species, is a trait associated with greater sensitivity and responsiveness to the environment and to social stimuli. Self-report studies have shown that high-SPS individuals are strongly affected by others' moods, but no previous study has examined neural systems engaged in response to others' emotions. This study examined the neural correlates of SPS (measured by the standard short-form Highly Sensitive Person [HSP] scale) among 18 participants (10 females) while viewing photos of their romantic partners and of strangers displaying positive, negative, or neutral facial expressions. One year apart, 13 of the 18 participants were scanned twice. Across all conditions, HSP scores were associated with increased brain activation of regions involved in attention and action planning (in the cingulate and premotor area [PMA]). For happy and sad photo conditions, SPS was associated with activation of brain regions involved in awareness, integration of sensory information, empathy, and action planning (e.g., cingulate, insula, inferior frontal gyrus [IFG], middle temporal gyrus [MTG], and PMA). As predicted, for partner images and for happy facial photos, HSP scores were associated with stronger activation of brain regions involved in awareness, empathy, and self-other processing. These results provide evidence that awareness and responsiveness are fundamental features of SPS, and show how the brain may mediate these traits.

The highly sensitive brain: an fMRI study of sensory processing sensitivity and response to others' emotions

PubMed Central

Acevedo, Bianca P; Aron, Elaine N; Aron, Arthur; Sangster, Matthew-Donald; Collins, Nancy; Brown, Lucy L

2014-01-01

Background Theory and research suggest that sensory processing sensitivity (SPS), found in roughly 20% of humans and over 100 other species, is a trait associated with greater sensitivity and responsiveness to the environment and to social stimuli. Self-report studies have shown that high-SPS individuals are strongly affected by others' moods, but no previous study has examined neural systems engaged in response to others' emotions. Methods This study examined the neural correlates of SPS (measured by the standard short-form Highly Sensitive Person [HSP] scale) among 18 participants (10 females) while viewing photos of their romantic partners and of strangers displaying positive, negative, or neutral facial expressions. One year apart, 13 of the 18 participants were scanned twice. Results Across all conditions, HSP scores were associated with increased brain activation of regions involved in attention and action planning (in the cingulate and premotor area [PMA]). For happy and sad photo conditions, SPS was associated with activation of brain regions involved in awareness, integration of sensory information, empathy, and action planning (e.g., cingulate, insula, inferior frontal gyrus [IFG], middle temporal gyrus [MTG], and PMA). Conclusions As predicted, for partner images and for happy facial photos, HSP scores were associated with stronger activation of brain regions involved in awareness, empathy, and self-other processing. These results provide evidence that awareness and responsiveness are fundamental features of SPS, and show how the brain may mediate these traits. PMID:25161824

Finite element modeling of human brain response to football helmet impacts.

PubMed

Darling, T; Muthuswamy, J; Rajan, S D

2016-10-01

The football helmet is used to help mitigate the occurrence of impact-related traumatic (TBI) and minor traumatic brain injuries (mTBI) in the game of American football. While the current helmet design methodology may be adequate for reducing linear acceleration of the head and minimizing TBI, it however has had less effect in minimizing mTBI. The objectives of this study are (a) to develop and validate a coupled finite element (FE) model of a football helmet and the human body, and (b) to assess responses of different regions of the brain to two different impact conditions - frontal oblique and crown impact conditions. The FE helmet model was validated using experimental results of drop tests. Subsequently, the integrated helmet-human body FE model was used to assess the responses of different regions of the brain to impact loads. Strain-rate, strain, and stress measures in the corpus callosum, midbrain, and brain stem were assessed. Results show that maximum strain-rates of 27 and 19 s(-1) are observed in the brain-stem and mid-brain, respectively. This could potentially lead to axonal injuries and neuronal cell death during crown impact conditions. The developed experimental-numerical framework can be used in the study of other helmet-related impact conditions.

Segregating the significant from the mundane on a moment-to-moment basis via direct and indirect amygdala contributions

PubMed Central

Lim, Seung-Lark; Padmala, Srikanth; Pessoa, Luiz

2009-01-01

If the amygdala is involved in shaping perceptual experience when affectively significant visual items are encountered, responses in this structure should be correlated with both visual cortex responses and behavioral reports. Here, we investigated how affective significance shapes visual perception during an attentional blink paradigm combined with aversive conditioning. Behaviorally, following aversive learning, affectively significant scenes (CS+) were better detected than neutral (CS−) ones. In terms of mean brain responses, both amygdala and visual cortical responses were stronger during CS+ relative to CS− trials. Increased brain responses in these regions were associated with improved behavioral performance across participants and followed a mediation-like pattern. Importantly, the mediation pattern was observed in a trial-by-trial analysis, revealing that the specific pattern of trial-by-trial variability in brain responses was closely related to single-trial behavioral performance. Furthermore, the influence of the amygdala on visual cortical responses was consistent with a mediation, although partial, via frontal brain regions. Our results thus suggest that affective significance potentially determines the fate of a visual item during competitive interactions by enhancing sensory processing through both direct and indirect paths. In so doing, the amygdala helps separate the significant from the mundane. PMID:19805383

Neuronal chronometry of target detection: fusion of hemodynamic and event-related potential data.

PubMed

Calhoun, V D; Adali, T; Pearlson, G D; Kiehl, K A

2006-04-01

Event-related potential (ERP) studies of the brain's response to infrequent, target (oddball) stimuli elicit a sequence of physiological events, the most prominent and well studied being a complex, the P300 (or P3) peaking approximately 300 ms post-stimulus for simple stimuli and slightly later for more complex stimuli. Localization of the neural generators of the human oddball response remains challenging due to the lack of a single imaging technique with good spatial and temporal resolution. Here, we use independent component analyses to fuse ERP and fMRI modalities in order to examine the dynamics of the auditory oddball response with high spatiotemporal resolution across the entire brain. Initial activations in auditory and motor planning regions are followed by auditory association cortex and motor execution regions. The P3 response is associated with brainstem, temporal lobe, and medial frontal activity and finally a late temporal lobe "evaluative" response. We show that fusing imaging modalities with different advantages can provide new information about the brain.

Neurovascular regulation in the ischemic brain.

PubMed

Jackman, Katherine; Iadecola, Costantino

2015-01-10

The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active responses such as cerebral autoregulation, which acts to maintain constant cerebral blood flow in response to changing blood pressure, and functional hyperemia, which couples blood supply with synaptic activity, allow the brain to maintain adequate cerebral perfusion in the face of varying supply or demand. In the presence of stroke risk factors, such as hypertension and diabetes, these protective processes are impaired and the susceptibility of the brain to ischemic injury is increased. One potential mechanism for the increased injury is that collateral flow arising from the normally perfused brain and supplying blood flow to the ischemic region is suppressed, resulting in more severe ischemia. Approaches to support collateral flow may ameliorate the outcome of focal cerebral ischemia by rescuing cerebral perfusion in potentially viable regions of the ischemic territory.

Region specific changes in nonapeptide levels during client fish interactions with allopatric and sympatric cleaner fish

PubMed Central

Soares, Marta C.; Cardoso, Sónia C.; Mazzei, Renata; André, Gonçalo I.; Morais, Marta; Gozdowska, Magdalena; Kalamarz-Kubiak, Hanna; Kulczykowska, Ewa

2017-01-01

Social relationships are crucially dependent on individual ability to learn and remember ecologically relevant cues. However, the way animals recognize cues before engaging in any social interaction and how their response is regulated by brain neuromodulators remains unclear. We examined the putative involvement of arginine vasotocin (AVT) and isotocin (IT), acting at different brain regions, during fish decision-making in the context of cooperation, by trying to identify how fish distinguish and recognize the value of other social partners or species. We hypothesized that the behavioural responses of cleaner fish clients to different social contexts would be underlain by changes in brain AVT and IT levels. We have found that changes in AVT at the level of forebrain and optic tectum are linked with a response to allopatric cleaners (novel or unfamiliar stimuli) while those at cerebellum are associated with the willingness to be cleaned (in response to sympatric cleaners). On the other hand, higher brain IT levels that were solely found in the diencephalon, also in response to allopatric cleaners. Our results are the first to implicate these nonapeptides, AVT in particular, in the assessment of social cues which enable fish to engage in mutualistic activities. PMID:28683143

Decoding negative affect personality trait from patterns of brain activation to threat stimuli.

PubMed

Fernandes, Orlando; Portugal, Liana C L; Alves, Rita de Cássia S; Arruda-Sanchez, Tiago; Rao, Anil; Volchan, Eliane; Pereira, Mirtes; Oliveira, Letícia; Mourao-Miranda, Janaina

2017-01-15

Pattern recognition analysis (PRA) applied to functional magnetic resonance imaging (fMRI) has been used to decode cognitive processes and identify possible biomarkers for mental illness. In the present study, we investigated whether the positive affect (PA) or negative affect (NA) personality traits could be decoded from patterns of brain activation in response to a human threat using a healthy sample. fMRI data from 34 volunteers (15 women) were acquired during a simple motor task while the volunteers viewed a set of threat stimuli that were directed either toward them or away from them and matched neutral pictures. For each participant, contrast images from a General Linear Model (GLM) between the threat versus neutral stimuli defined the spatial patterns used as input to the regression model. We applied a multiple kernel learning (MKL) regression combining information from different brain regions hierarchically in a whole brain model to decode the NA and PA from patterns of brain activation in response to threat stimuli. The MKL model was able to decode NA but not PA from the contrast images between threat stimuli directed away versus neutral with a significance above chance. The correlation and the mean squared error (MSE) between predicted and actual NA were 0.52 (p-value=0.01) and 24.43 (p-value=0.01), respectively. The MKL pattern regression model identified a network with 37 regions that contributed to the predictions. Some of the regions were related to perception (e.g., occipital and temporal regions) while others were related to emotional evaluation (e.g., caudate and prefrontal regions). These results suggest that there was an interaction between the individuals' NA and the brain response to the threat stimuli directed away, which enabled the MKL model to decode NA from the brain patterns. To our knowledge, this is the first evidence that PRA can be used to decode a personality trait from patterns of brain activation during emotional contexts. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Moral concepts set decision strategies to abstract values.

PubMed

Caspers, Svenja; Heim, Stefan; Lucas, Marc G; Stephan, Egon; Fischer, Lorenz; Amunts, Katrin; Zilles, Karl

2011-04-01

Persons have different value preferences. Neuroimaging studies where value-based decisions in actual conflict situations were investigated suggest an important role of prefrontal and cingulate brain regions. General preferences, however, reflect a superordinate moral concept independent of actual situations as proposed in psychological and socioeconomic research. Here, the specific brain response would be influenced by abstract value systems and moral concepts. The neurobiological mechanisms underlying such responses are largely unknown. Using functional magnetic resonance imaging (fMRI) with a forced-choice paradigm on word pairs representing abstract values, we show that the brain handles such decisions depending on the person's superordinate moral concept. Persons with a predominant collectivistic (altruistic) value system applied a "balancing and weighing" strategy, recruiting brain regions of rostral inferior and intraparietal, and midcingulate and frontal cortex. Conversely, subjects with mainly individualistic (egocentric) value preferences applied a "fight-and-flight" strategy by recruiting the left amygdala. Finally, if subjects experience a value conflict when rejecting an alternative congruent to their own predominant value preference, comparable brain regions are activated as found in actual moral dilemma situations, i.e., midcingulate and dorsolateral prefrontal cortex. Our results demonstrate that superordinate moral concepts influence the strategy and the neural mechanisms in decision processes, independent of actual situations, showing that decisions are based on general neural principles. These findings provide a novel perspective to future sociological and economic research as well as to the analysis of social relations by focusing on abstract value systems as triggers of specific brain responses.

Moral Concepts Set Decision Strategies to Abstract Values

PubMed Central

Caspers, Svenja; Heim, Stefan; Lucas, Marc G.; Stephan, Egon; Fischer, Lorenz; Amunts, Katrin; Zilles, Karl

2011-01-01

Persons have different value preferences. Neuroimaging studies where value-based decisions in actual conflict situations were investigated suggest an important role of prefrontal and cingulate brain regions. General preferences, however, reflect a superordinate moral concept independent of actual situations as proposed in psychological and socioeconomic research. Here, the specific brain response would be influenced by abstract value systems and moral concepts. The neurobiological mechanisms underlying such responses are largely unknown. Using functional magnetic resonance imaging (fMRI) with a forced-choice paradigm on word pairs representing abstract values, we show that the brain handles such decisions depending on the person's superordinate moral concept. Persons with a predominant collectivistic (altruistic) value system applied a “balancing and weighing” strategy, recruiting brain regions of rostral inferior and intraparietal, and midcingulate and frontal cortex. Conversely, subjects with mainly individualistic (egocentric) value preferences applied a “fight-and-flight” strategy by recruiting the left amygdala. Finally, if subjects experience a value conflict when rejecting an alternative congruent to their own predominant value preference, comparable brain regions are activated as found in actual moral dilemma situations, i.e., midcingulate and dorsolateral prefrontal cortex. Our results demonstrate that superordinate moral concepts influence the strategy and the neural mechanisms in decision processes, independent of actual situations, showing that decisions are based on general neural principles. These findings provide a novel perspective to future sociological and economic research as well as to the analysis of social relations by focusing on abstract value systems as triggers of specific brain responses. PMID:21483767

Sexual selection predicts brain structure in dragon lizards.

PubMed

Hoops, D; Ullmann, J F P; Janke, A L; Vidal-Garcia, M; Stait-Gardner, T; Dwihapsari, Y; Merkling, T; Price, W S; Endler, J A; Whiting, M J; Keogh, J S

2017-02-01

Phenotypic traits such as ornaments and armaments are generally shaped by sexual selection, which often favours larger and more elaborate males compared to females. But can sexual selection also influence the brain? Previous studies in vertebrates report contradictory results with no consistent pattern between variation in brain structure and the strength of sexual selection. We hypothesize that sexual selection will act in a consistent way on two vertebrate brain regions that directly regulate sexual behaviour: the medial preoptic nucleus (MPON) and the ventromedial hypothalamic nucleus (VMN). The MPON regulates male reproductive behaviour whereas the VMN regulates female reproductive behaviour and is also involved in male aggression. To test our hypothesis, we used high-resolution magnetic resonance imaging combined with traditional histology of brains in 14 dragon lizard species of the genus Ctenophorus that vary in the strength of precopulatory sexual selection. Males belonging to species that experience greater sexual selection had a larger MPON and a smaller VMN. Conversely, females did not show any patterns of variation in these brain regions. As the volumes of both these regions also correlated with brain volume (BV) in our models, we tested whether they show the same pattern of evolution in response to changes in BV and found that the do. Therefore, we show that the primary brain nuclei underlying reproductive behaviour in vertebrates can evolve in a mosaic fashion, differently between males and females, likely in response to sexual selection, and that these same regions are simultaneously evolving in concert in relation to overall brain size. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

The impact of hypoglycaemia awareness status on regional brain responses to acute hypoglycaemia in men with type 1 diabetes.

PubMed

Dunn, Joel T; Choudhary, Pratik; Teh, Ming Ming; Macdonald, Ian; Hunt, Katharine F; Marsden, Paul K; Amiel, Stephanie A

2018-05-12

Impaired awareness of hypoglycaemia (IAH) in type 1 diabetes increases the risk of severe hypoglycaemia sixfold and can be resistant to intervention. We explored the impact of IAH on central responses to hypoglycaemia to investigate the mechanisms underlying barriers to therapeutic intervention. We conducted [ 15 O]water positron emission tomography studies of regional brain perfusion during euglycaemia (target 5 mmol/l), hypoglycaemia (achieved level, 2.4 mmol/l) and recovery (target 5 mmol/l) in 17 men with type 1 diabetes: eight with IAH, and nine with intact hypoglycaemia awareness (HA). Hypoglycaemia with HA was associated with increased activation in brain regions including the thalamus, insula, globus pallidus (GP), anterior cingulate cortex (ACC), orbital cortex, dorsolateral frontal (DLF) cortex, angular gyrus and amygdala; deactivation occurred in the temporal and parahippocampal regions. IAH was associated with reduced catecholamine and symptom responses to hypoglycaemia vs HA (incremental AUC: autonomic scores, 26.2 ± 35.5 vs 422.7 ± 237.1; neuroglycopenic scores, 34.8 ± 88.8 vs 478.9 ± 311.1; both p < 0.002). There were subtle differences (p < 0.005, k ≥ 50 voxels) in brain activation at hypoglycaemia, including early differences in the right central operculum, bilateral medial orbital (MO) cortex, and left posterior DLF cortex, with additional differences in the ACC, right GP and post- and pre-central gyri in established hypoglycaemia, and lack of deactivation in temporal regions in established hypoglycaemia. Differences in activation in the post- and pre-central gyri may be expected in people with reduced subjective responses to hypoglycaemia. Alterations in the activity of regions involved in the drive to eat (operculum), emotional salience (MO cortex), aversion (GP) and recall (temporal) suggest differences in the perceived importance and urgency of responses to hypoglycaemia in IAH compared with HA, which may be key to the persistence of the condition.

Vulnerability of the developing brain to hypoxic-ischemic damage: contribution of the cerebral vasculature to injury and repair?

PubMed Central

Baburamani, Ana A.; Ek, C. Joakim; Walker, David W.; Castillo-Melendez, Margie

2012-01-01

As clinicians attempt to understand the underlying reasons for the vulnerability of different regions of the developing brain to injury, it is apparent that little is known as to how hypoxia-ischemia may affect the cerebrovasculature in the developing infant. Most of the research investigating the pathogenesis of perinatal brain injury following hypoxia-ischemia has focused on excitotoxicity, oxidative stress and an inflammatory response, with the response of the developing cerebrovasculature receiving less attention. This is surprising as the presentation of devastating and permanent injury such as germinal matrix-intraventricular haemorrhage (GM-IVH) and perinatal stroke are of vascular origin, and the origin of periventricular leukomalacia (PVL) may also arise from poor perfusion of the white matter. This highlights that cerebrovasculature injury following hypoxia could primarily be responsible for the injury seen in the brain of many infants diagnosed with hypoxic-ischemic encephalopathy (HIE). Interestingly the highly dynamic nature of the cerebral blood vessels in the fetus, and the fluctuations of cerebral blood flow and metabolic demand that occur following hypoxia suggest that the response of blood vessels could explain both regional protection and vulnerability in the developing brain. However, research into how blood vessels respond following hypoxia-ischemia have mostly been conducted in adult models of ischemia or stroke, further highlighting the need to investigate how the developing cerebrovasculature responds and the possible contribution to perinatal brain injury following hypoxia. This review discusses the current concepts on the pathogenesis of perinatal brain injury, the development of the fetal cerebrovasculature and the blood brain barrier (BBB), and key mediators involved with the response of cerebral blood vessels to hypoxia. PMID:23162470

THE THYROID HORMONE TRANSPORTER, MCT8, SELECTIVELY RESPONDS TO THYROID HORMONE INSUFFICIENCY IN THE DEVELOPMENT RAT BRAIN.

EPA Science Inventory

Thyroid hormone (TH) is essential for normal brain development. Therefore, it is not surprising that a variety of adaptive mechanisms are activated in response to TH insufficiency. However, not all brain regions respond in the same fashion to TH insufficiency. This observation...

Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

PubMed

Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

2012-01-01

Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and represent important end-points for analysis in studies of therapeutic strategies to protect patients from neural dysfunction.

Tyrosine hydroxylase expression and activity in the rat brain: differential regulation after long-term intermittent or sustained hypoxia.

PubMed

Gozal, Evelyne; Shah, Zahoor A; Pequignot, Jean-Marc; Pequignot, Jacqueline; Sachleben, Leroy R; Czyzyk-Krzeska, Maria F; Li, Richard C; Guo, Shang-Z; Gozal, David

2005-08-01

Tyrosine hydroxylase, a hypoxia-regulated gene, may be involved in tissue adaptation to hypoxia. Intermittent hypoxia, a characteristic feature of sleep apnea, leads to significant memory deficits, as well as to cortex and hippocampal apoptosis that are absent after sustained hypoxia. To examine the hypothesis that sustained and intermittent hypoxia induce different catecholaminergic responses, changes in tyrosine hydroxylase mRNA, protein expression, and activity were compared in various brain regions of male rats exposed for 6 h, 1 day, 3 days, and 7 days to sustained hypoxia (10% O(2)), intermittent hypoxia (alternating room air and 10% O(2)), or normoxia. Tyrosine hydroxylase activity, measured at 7 days, increased in the cortex as follows: sustained > intermittent > normoxia. Furthermore, activity decreased in the brain stem and was unchanged in other brain regions of sustained hypoxia-exposed rats, as well as in all regions from animals exposed to intermittent hypoxia, suggesting stimulus-specific and heterotopic catecholamine regulation. In the cortex, tyrosine hydroxylase mRNA expression was increased, whereas protein expression remained unchanged. In addition, significant differences in the time course of cortical Ser(40) tyrosine hydroxylase phosphorylation were present in the cortex, suggesting that intermittent and sustained hypoxia-induced enzymatic activity differences are related to different phosphorylation patterns. We conclude that long-term hypoxia induces site-specific changes in tyrosine hydroxylase activity and that intermittent hypoxia elicits reduced tyrosine hydroxylase recruitment and phosphorylation compared with sustained hypoxia. Such changes may not only account for differences in enzyme activity but also suggest that, with differential regional brain susceptibility to hypoxia, recruitment of different mechanisms in response to hypoxia will elicit region-specific modulation of catecholamine response.

Regional brain injury on conventional and diffusion weighted MRI is associated with outcome after pediatric cardiac arrest.

PubMed

Fink, Ericka L; Panigrahy, A; Clark, R S B; Fitz, C R; Landsittel, D; Kochanek, P M; Zuccoli, G

2013-08-01

To assess regional brain injury on magnetic resonance imaging (MRI) after pediatric cardiac arrest (CA) and to associate regional injury with patient outcome and effects of hypothermia therapy for neuroprotection. We performed a retrospective chart review with prospective imaging analysis. Children between 1 week and 17 years of age who had a brain MRI in the first 2 weeks after CA without other acute brain injury between 2002 and 2008 were included. Brain MRI (1.5 T General Electric, Milwaukee, WI, USA) images were analyzed by 2 blinded neuroradiologists with adjudication; images were visually graded. Brain lobes, basal ganglia, thalamus, brain stem, and cerebellum were analyzed using T1, T2, and diffusion-weighted images (DWI). We examined 28 subjects with median age 1.9 years (IQR 0.4-13.0) and 19 (68 %) males. Increased intensity on T2 in the basal ganglia and restricted diffusion in the brain lobes were associated with unfavorable outcome (all P < 0.05). Therapeutic hypothermia had no effect on regional brain injury. Repeat brain MRI was infrequently performed but demonstrated evolution of lesions. Children with lesions in the basal ganglia on conventional MRI and brain lobes on DWI within the first 2 weeks after CA represent a group with increased risk of poor outcome. These findings may be important for developing neuroprotective strategies based on regional brain injury and for evaluating response to therapy in interventional clinical trials.

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

Michaelides, M.; Wang, G.; Michaelides, M.

Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated imagemore » registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.« less

Repeated exposure to sublethal doses of the organophosphorus compound VX activates BDNF expression in mouse brain.

PubMed

Pizarro, Jose M; Chang, Wenling E; Bah, Mariama J; Wright, Linnzi K M; Saviolakis, George A; Alagappan, Arun; Robison, Christopher L; Shah, Jinesh D; Meyerhoff, James L; Cerasoli, Douglas M; Midboe, Eric G; Lumley, Lucille A

2012-04-01

The highly toxic organophosphorus compound VX [O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonate] is an irreversible inhibitor of the enzyme acetylcholinesterase (AChE). Prolonged inhibition of AChE increases endogenous levels of acetylcholine and is toxic at nerve synapses and neuromuscular junctions. We hypothesized that repeated exposure to sublethal doses of VX would affect genes associated with cell survival, neuronal plasticity, and neuronal remodeling, including brain-derived neurotrophic factor (BDNF). We examined the time course of BDNF expression in C57BL/6 mouse brain following repeated exposure (1/day × 5 days/week × 2 weeks) to sublethal doses of VX (0.2 LD(50) and 0.4 LD(50)). BDNF messenger RNA expression was significantly (p < 0.05) elevated in multiple brain regions, including the dentate gyrus, CA3, and CA1 regions of the hippocampal formation, as well as the piriform cortex, hypothalamus, amygdala, and thalamus, 72 h after the last 0.4 LD(50) VX exposure. BDNF protein expression, however, was only increased in the CA3 region of the hippocampus. Whether increased BDNF in response to sublethal doses of VX exposure is an adaptive response to prevent cellular damage or a precursor to impending brain damage remains to be determined. If elevated BDNF is an adaptive response, exogenous BDNF may be a potential therapeutic target to reduce the toxic effects of nerve agent exposure.

Neural Representation of Subjective Sexual Arousal in Men and Women.

PubMed

Parada, Mayte; Gérard, Marina; Larcher, Kevin; Dagher, Alain; Binik, Yitzchak M

2016-10-01

Studies investigating brain indices of sexual arousal have begun to elucidate the brain's role in processing subjective arousal; however, most research has focused on men, used discrete ratings of subjective arousal, and used stimuli too short to induce significant arousal in women. To examine brain regions modulated by changes in subjective sexual arousal (SSA) rating intensity in men and women. Two groups (20 men, 20 women) viewed movie clips (erotic or humorous) while continuously evaluating changes in their SSA using a Likert-like scale (0 = not aroused, 10 = most aroused) and answering discrete questions about liking the movies and wanting sexual stimulation. Brain activity was measured using functional magnetic resonance imaging. Blood oxygen level-dependent responses and continuous and discrete measurements of sexual arousal. Erotic movies induced significant SSA in men and women. No sex difference in mean SSA was found in response to the erotic movies on continuous or discrete measurements. Several brain regions were correlated with changes in SSA. Parametric modulation with rating intensity showed a specific group of regions within the parietal lobe that showed significant differences in activity among low, medium, and high SSA. Multiple regions were concordant with changes in SSA; however, a subset of regions in men and women was modulated by SSA intensity, a subset previously linked to attentional processes, monitoring of internal body representation, and processing of sensory information from the genitals. This study highlights that similar brain regions are activated during subjective assessment of sexual arousal in men and women. The data further highlight the fact that SSA is a complex phenomenon made up of multiple interoceptive and attentional processes. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Serial MR diffusion to predict treatment response in high-grade pediatric brain tumors: a comparison of regional and voxel-based diffusion change metrics

PubMed Central

Rodriguez Gutierrez, Daniel; Manita, Muftah; Jaspan, Tim; Dineen, Robert A.; Grundy, Richard G.; Auer, Dorothee P.

2013-01-01

Background Assessment of treatment response by measuring tumor size is known to be a late and potentially confounded response index. Serial diffusion MRI has shown potential for allowing earlier and possibly more reliable response assessment in adult patients, with limited experience in clinical settings and in pediatric brain cancer. We present a retrospective study of clinical MRI data in children with high-grade brain tumors to assess and compare the values of several diffusion change metrics to predict treatment response. Methods Eighteen patients (age range, 1.9–20.6 years) with high-grade brain tumors and serial diffusion MRI (pre- and posttreatment interval range, 1–16 weeks posttreatment) were identified after obtaining parental consent. The following diffusion change metrics were compared with the clinical response status assessed at 6 months: (1) regional change in absolute and normalized apparent diffusivity coefficient (ADC), (2) voxel-based fractional volume of increased (fiADC) and decreased ADC (fdADC), and (3) a new metric based on the slope of the first principal component of functional diffusion maps (fDM). Results Responders (n = 12) differed significantly from nonresponders (n = 6) in all 3 diffusional change metrics demonstrating higher regional ADC increase, larger fiADC, and steeper slopes (P < .05). The slope method allowed the best response prediction (P < .01, η2 = 0.78) with a classification accuracy of 83% for a slope of 58° using receiver operating characteristic (ROC) analysis. Conclusions We demonstrate that diffusion change metrics are suitable response predictors for high-grade pediatric tumors, even in the presence of variable clinical diffusion imaging protocols. PMID:23585630

Voxel-based analysis of the immediate early gene, c-jun, in the honey bee brain after a sucrose stimulus.

PubMed

McNeill, M S; Robinson, G E

2015-06-01

Immediate early genes (IEGs) have served as useful markers of brain neuronal activity in mammals, and more recently in insects. The mammalian canonical IEG, c-jun, is part of regulatory pathways conserved in insects and has been shown to be responsive to alarm pheromone in honey bees. We tested whether c-jun was responsive in honey bees to another behaviourally relevant stimulus, sucrose, in order to further identify the brain regions involved in sucrose processing. To identify responsive regions, we developed a new method of voxel-based analysis of c-jun mRNA expression. We found that c-jun is expressed in somata throughout the brain. It was rapidly induced in response to sucrose stimuli, and it responded in somata near the antennal and mechanosensory motor centre, mushroom body calices and lateral protocerebrum, which are known to be involved in sucrose processing. c-jun also responded to sucrose in somata near the lateral suboesophageal ganglion, dorsal optic lobe, ventral optic lobe and dorsal posterior protocerebrum, which had not been previously identified by other methods. These results demonstrate the utility of voxel-based analysis of mRNA expression in the insect brain. © 2015 The Royal Entomological Society.

Noninvasive monitoring of treatment response in a rabbit cyanide toxicity model reveals differences in brain and muscle metabolism

NASA Astrophysics Data System (ADS)

Kim, Jae G.; Lee, Jangwoen; Mahon, Sari B.; Mukai, David; Patterson, Steven E.; Boss, Gerry R.; Tromberg, Bruce J.; Brenner, Matthew

2012-10-01

Noninvasive near infrared spectroscopy measurements were performed to monitor cyanide (CN) poisoning and recovery in the brain region and in foreleg muscle simultaneously, and the effects of a novel CN antidote, sulfanegen sodium, on tissue hemoglobin oxygenation changes were compared using a sub-lethal rabbit model. The results demonstrated that the brain region is more susceptible to CN poisoning and slower in endogenous CN detoxification following exposure than peripheral muscles. However, sulfanegen sodium rapidly reversed CN toxicity, with brain region effects reversing more quickly than muscle. In vivo monitoring of multiple organs may provide important clinical information regarding the extent of CN toxicity and subsequent recovery, and facilitate antidote drug development.

Brain, body, and cognition: Neural, physiological and self-report correlates of phobic and normative fear

PubMed Central

Schaefer, Hillary S.; Larson, Christine L.; Davidson, Richard J.; Coan, James A.

2014-01-01

The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction. PMID:24561099

Brain, body, and cognition: neural, physiological and self-report correlates of phobic and normative fear.

PubMed

Schaefer, Hillary S; Larson, Christine L; Davidson, Richard J; Coan, James A

2014-04-01

The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction. Copyright © 2014. Published by Elsevier B.V.

Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women.

PubMed

Li, Bingbing; Cheng, Gang; Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

2016-01-01

Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects' Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and perspective taking ability.

Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women

PubMed Central

Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

2016-01-01

Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects’ Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and perspective taking ability. PMID:27977692

Functional selectivity for face processing in the temporal voice area of early deaf individuals

PubMed Central

van Ackeren, Markus J.; Rabini, Giuseppe; Zonca, Joshua; Foa, Valentina; Baruffaldi, Francesca; Rezk, Mohamed; Pavani, Francesco; Rossion, Bruno; Collignon, Olivier

2017-01-01

Brain systems supporting face and voice processing both contribute to the extraction of important information for social interaction (e.g., person identity). How does the brain reorganize when one of these channels is absent? Here, we explore this question by combining behavioral and multimodal neuroimaging measures (magneto-encephalography and functional imaging) in a group of early deaf humans. We show enhanced selective neural response for faces and for individual face coding in a specific region of the auditory cortex that is typically specialized for voice perception in hearing individuals. In this region, selectivity to face signals emerges early in the visual processing hierarchy, shortly after typical face-selective responses in the ventral visual pathway. Functional and effective connectivity analyses suggest reorganization in long-range connections from early visual areas to the face-selective temporal area in individuals with early and profound deafness. Altogether, these observations demonstrate that regions that typically specialize for voice processing in the hearing brain preferentially reorganize for face processing in born-deaf people. Our results support the idea that cross-modal plasticity in the case of early sensory deprivation relates to the original functional specialization of the reorganized brain regions. PMID:28652333

Increased Sleep Depth in Developing Neural Networks: New Insights from Sleep Restriction in Children

PubMed Central

Kurth, Salome; Dean, Douglas C.; Achermann, Peter; O’Muircheartaigh, Jonathan; Huber, Reto; Deoni, Sean C. L.; LeBourgeois, Monique K.

2016-01-01

Brain networks respond to sleep deprivation or restriction with increased sleep depth, which is quantified as slow-wave activity (SWA) in the sleep electroencephalogram (EEG). When adults are sleep deprived, this homeostatic response is most pronounced over prefrontal brain regions. However, it is unknown how children’s developing brain networks respond to acute sleep restriction, and whether this response is linked to myelination, an ongoing process in childhood that is critical for brain development and cortical integration. We implemented a bedtime delay protocol in 5- to 12-year-old children to obtain partial sleep restriction (1-night; 50% of their habitual sleep). High-density sleep EEG was assessed during habitual and restricted sleep and brain myelin content was obtained using mcDESPOT magnetic resonance imaging. The effect of sleep restriction was analyzed using statistical non-parametric mapping with supra-threshold cluster analysis. We observed a localized homeostatic SWA response following sleep restriction in a specific parieto-occipital region. The restricted/habitual SWA ratio was negatively associated with myelin water fraction in the optic radiation, a developing fiber bundle. This relationship occurred bilaterally over parieto-temporal areas and was adjacent to, but did not overlap with the parieto-occipital region showing the most pronounced homeostatic SWA response. These results provide evidence for increased sleep need in posterior neural networks in children. Sleep need in parieto-temporal areas is related to myelin content, yet it remains speculative whether age-related myelin growth drives the fading of the posterior homeostatic SWA response during the transition to adulthood. Whether chronic insufficient sleep in the sensitive period of early life alters the anatomical generators of deep sleep slow-waves is an important unanswered question. PMID:27708567

Preserved Haptic Shape Processing after Bilateral LOC Lesions.

PubMed

Snow, Jacqueline C; Goodale, Melvyn A; Culham, Jody C

2015-10-07

The visual and haptic perceptual systems are understood to share a common neural representation of object shape. A region thought to be critical for recognizing visual and haptic shape information is the lateral occipital complex (LOC). We investigated whether LOC is essential for haptic shape recognition in humans by studying behavioral responses and brain activation for haptically explored objects in a patient (M.C.) with bilateral lesions of the occipitotemporal cortex, including LOC. Despite severe deficits in recognizing objects using vision, M.C. was able to accurately recognize objects via touch. M.C.'s psychophysical response profile to haptically explored shapes was also indistinguishable from controls. Using fMRI, M.C. showed no object-selective visual or haptic responses in LOC, but her pattern of haptic activation in other brain regions was remarkably similar to healthy controls. Although LOC is routinely active during visual and haptic shape recognition tasks, it is not essential for haptic recognition of object shape. The lateral occipital complex (LOC) is a brain region regarded to be critical for recognizing object shape, both in vision and in touch. However, causal evidence linking LOC with haptic shape processing is lacking. We studied recognition performance, psychophysical sensitivity, and brain response to touched objects, in a patient (M.C.) with extensive lesions involving LOC bilaterally. Despite being severely impaired in visual shape recognition, M.C. was able to identify objects via touch and she showed normal sensitivity to a haptic shape illusion. M.C.'s brain response to touched objects in areas of undamaged cortex was also very similar to that observed in neurologically healthy controls. These results demonstrate that LOC is not necessary for recognizing objects via touch. Copyright © 2015 the authors 0270-6474/15/3513745-16$15.00/0.

Decoding Articulatory Features from fMRI Responses in Dorsal Speech Regions.

PubMed

Correia, Joao M; Jansma, Bernadette M B; Bonte, Milene

2015-11-11

The brain's circuitry for perceiving and producing speech may show a notable level of overlap that is crucial for normal development and behavior. The extent to which sensorimotor integration plays a role in speech perception remains highly controversial, however. Methodological constraints related to experimental designs and analysis methods have so far prevented the disentanglement of neural responses to acoustic versus articulatory speech features. Using a passive listening paradigm and multivariate decoding of single-trial fMRI responses to spoken syllables, we investigated brain-based generalization of articulatory features (place and manner of articulation, and voicing) beyond their acoustic (surface) form in adult human listeners. For example, we trained a classifier to discriminate place of articulation within stop syllables (e.g., /pa/ vs /ta/) and tested whether this training generalizes to fricatives (e.g., /fa/ vs /sa/). This novel approach revealed generalization of place and manner of articulation at multiple cortical levels within the dorsal auditory pathway, including auditory, sensorimotor, motor, and somatosensory regions, suggesting the representation of sensorimotor information. Additionally, generalization of voicing included the right anterior superior temporal sulcus associated with the perception of human voices as well as somatosensory regions bilaterally. Our findings highlight the close connection between brain systems for speech perception and production, and in particular, indicate the availability of articulatory codes during passive speech perception. Sensorimotor integration is central to verbal communication and provides a link between auditory signals of speech perception and motor programs of speech production. It remains highly controversial, however, to what extent the brain's speech perception system actively uses articulatory (motor), in addition to acoustic/phonetic, representations. In this study, we examine the role of articulatory representations during passive listening using carefully controlled stimuli (spoken syllables) in combination with multivariate fMRI decoding. Our approach enabled us to disentangle brain responses to acoustic and articulatory speech properties. In particular, it revealed articulatory-specific brain responses of speech at multiple cortical levels, including auditory, sensorimotor, and motor regions, suggesting the representation of sensorimotor information during passive speech perception. Copyright © 2015 the authors 0270-6474/15/3515015-11$15.00/0.

Dynamic pupillary exchange engages brain regions encoding social salience

PubMed Central

Harrison, Neil A.; Gray, Marcus A.; Critchley, Hugo D.

2008-01-01

Covert exchange of autonomic responses may shape social affective behavior, as observed in mirroring of pupillary responses during sadness processing. We examined how, independent of facial emotional expression, dynamic coherence between one's own and another's pupil size modulates regional brain activity. Fourteen subjects viewed pairs of eye stimuli while undergoing fMRI. Using continuous pupillometry biofeedback, the size of the observed pupils was varied, correlating positively or negatively with changes in participants’ own pupils. Viewing both static and dynamic stimuli activated right fusiform gyrus. Observing dynamically changing pupils activated STS and amygdala, regions engaged by non-static and salient facial features. Discordance between observed and observer's pupillary changes enhanced activity within bilateral anterior insula, left amygdala and anterior cingulate. In contrast, processing positively correlated pupils enhanced activity within left frontal operculum. Our findings suggest pupillary signals are monitored continuously during social interactions and that incongruent changes activate brain regions involved in tracking motivational salience and attentionally meaningful information. Naturalistically, dynamic coherence in pupillary change follows fluctuations in ambient light. Correspondingly, in social contexts discordant pupil response is likely to reflect divergence of dispositional state. Our data provide empirical evidence for an autonomically mediated extension of forward models of motor control into social interaction. PMID:19048432

A preliminary study of the effects of working memory training on brain function.

PubMed

Stevens, Michael C; Gaynor, Alexandra; Bessette, Katie L; Pearlson, Godfrey D

2016-06-01

Working memory (WM) training improves WM ability in Attention-Deficit/Hyperactivity Disorder (ADHD), but its efficacy for non-cognitive ADHD impairments ADHD has been sharply debated. The purpose of this preliminary study was to characterize WM training-related changes in ADHD brain function and see if they were linked to clinical improvement. We examined 18 adolescents diagnosed with DSM-IV Combined-subtype ADHD before and after 25 sessions of WM training using a frequently employed approach (Cogmed™) using a nonverbal Sternberg WM fMRI task, neuropsychological tests, and participant- and parent-reports of ADHD symptom severity and associated functional impairment. Whole brain SPM8 analyses identified ADHD activation deficits compared to 18 non-ADHD control participants, then tested whether impaired ADHD frontoparietal brain activation would increase following WM training. Post hoc tests examined the relationships between neural changes and neurocognitive or clinical improvements. As predicted, WM training increased WM performance, ADHD clinical functioning, and WM-related ADHD brain activity in several frontal, parietal and temporal lobe regions. Increased left inferior frontal sulcus region activity was seen in all Encoding, Maintenance, and Retrieval Sternberg task phases. ADHD symptom severity improvements were most often positively correlated with activation gains in brain regions known to be engaged for WM-related executive processing; improvement of different symptom types had different neural correlates. The responsiveness of both amodal WM frontoparietal circuits and executive process-specific WM brain regions was altered by WM training. The latter might represent a promising, relatively unexplored treatment target for researchers seeking to optimize clinical response in ongoing ADHD WM training development efforts.

Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

PubMed

Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

2017-04-12

Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We found that social recognition memory is consolidated through CREB-meditated gene expression in the hippocampus, medial prefrontal cortex, anterior cingulate cortex (ACC), and amygdala. Importantly, network analyses based on c-fos expression suggest that functional connectivity of these four brain regions with other brain regions is increased with time spent in social investigation toward the generation of brain networks to consolidate social recognition memory. Furthermore, our findings suggest that hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. Copyright © 2017 the authors 0270-6474/17/374103-14$15.00/0.

Distinct Neural Stem Cell Populations Give Rise to Disparate Brain Tumors in Response to N-MYC

PubMed Central

Swartling, Fredrik J.; Savov, Vasil; Persson, Anders I.; Chen, Justin; Hackett, Christopher S.; Northcott, Paul A.; Grimmer, Matthew R.; Lau, Jasmine; Chesler, Louis; Perry, Arie; Phillips, Joanna J.; Taylor, Michael D.; Weiss, William A.

2012-01-01

SUMMARY The proto-oncogene MYCN is mis-expressed in various types of human brain tumors. To clarify how developmental and regional differences influence transformation, we transduced wild-type or mutationally-stabilized murine N-mycT58A into neural stem cells (NSCs) from perinatal murine cerebellum, brain stem and forebrain. Transplantation of N-mycWT NSCs was insufficient for tumor formation. N-mycT58A cerebellar and brain stem NSCs generated medulloblastoma/primitive neuroectodermal tumors, whereas forebrain NSCs developed diffuse glioma. Expression analyses distinguished tumors generated from these different regions, with tumors from embryonic versus postnatal cerebellar NSCs demonstrating SHH-dependence and SHH-independence, respectively. These differences were regulated in-part by the transcription factor SOX9, activated in the SHH subclass of human medulloblastoma. Our results demonstrate context-dependent transformation of NSCs in response to a common oncogenic signal. PMID:22624711

Blueberries and strawberries activate neuronal housekeeping in critical brain regions of stress-induced young rats

USDA-ARS?s Scientific Manuscript database

Dysfunctional autophagy, where accumulation of damaged or complex cellular components in neurons in response to sublethal cell stress has been implicated in an array of brain disorders. This phenomenon plays a pivotal role in aging, because of the increased vulnerability of the aging brain to incre...

The relationship between age and brain response to visual erotic stimuli in healthy heterosexual males.

PubMed

Seo, Y; Jeong, B; Kim, J-W; Choi, J

2010-01-01

The various changes of sexuality, including decreased sexual desire and erectile dysfunction, are also accompanied with aging. To understand the effect of aging on sexuality, we explored the relationship between age and the visual erotic stimulation-related brain response in sexually active male subjects. Twelve healthy, heterosexual male subjects (age 22-47 years) were recorded the functional magnetic resonance imaging (fMRI) signals of their brain activation elicited by passive viewing erotic (ERO), happy-faced (HA) couple, food and nature pictures. Mixed effect analysis and correlation analysis were performed to investigate the relationship between the age and the change of brain activity elicited by erotic stimuli. Our results showed age was positively correlated with the activation of right occipital fusiform gyrus and amygdala, and negatively correlated with the activation of right insula and inferior frontal gyrus. These findings suggest age might be related with functional decline in brain regions being involved in both interoceptive sensation and prefrontal modulation while it is related with the incremental activity of the brain region for early processing of visual emotional stimuli in sexually healthy men.

Ethanol self-administration and nicotine treatment increase brain levels of CYP2D in African green monkeys

PubMed Central

Miller, R T; Miksys, S; Hoffmann, E; Tyndale, R F

2014-01-01

BACKGROUND AND PURPOSE CYP2D6 metabolizes many centrally acting drugs, neurotoxins and endogenous neurochemicals, and differences in brain levels of CYP2D have been associated with brain function and drug response. Alcohol consumers and smokers have higher levels of CYP2D6 in brain, but not liver, suggesting ethanol and/or nicotine may induce human brain CYP2D6. We investigated the independent and combined effects of chronic ethanol self-administration and nicotine treatment on CYP2D expression in African green monkeys. EXPERIMENTAL APPROACH Forty monkeys were randomized into control, ethanol-only, nicotine-only and ethanol + nicotine groups. Two groups voluntarily self-administered 10% ethanol in sucrose solution for 4 h·day−1, whereas two groups consumed sucrose solution on the same schedule. Two groups received daily s.c. injections of 0.5 mg·kg−1 nicotine in saline bid, whereas two groups were injected with saline on the same schedule. KEY RESULTS Both nicotine and ethanol dose-dependently increased CYP2D in brain; brain mRNA was unaffected, and neither drug altered hepatic CYP2D protein or mRNA. The combination of ethanol and nicotine increased brain CYP2D protein levels to a greater extent than either drug alone (1.2–2.2-fold, P < 0.05 among the eight brain regions assessed). Immunohistochemistry revealed the induction of brain CYP2D protein within specific cell types and regions in the treatment groups. CONCLUSIONS AND IMPLICATIONS Ethanol and nicotine increase brain CYP2D protein levels in monkeys, in a region and treatment-specific manner, suggesting that CNS drug responses, neurodegeneration and personality may be affected among people who consume alcohol and/or nicotine. PMID:24611668

Differential Recruitment of Brain Regions During Response Inhibition in Children Prenatally Exposed to Alcohol.

PubMed

Kodali, Vikas N; Jacobson, Joseph L; Lindinger, Nadine M; Dodge, Neil C; Molteno, Christopher D; Meintjes, Ernesta M; Jacobson, Sandra W

2017-02-01

Response inhibition is a distinct aspect of executive function that is frequently impaired in children with fetal alcohol spectrum disorders (FASD). We used a Go/NoGo (GNG) task in a functional MRI protocol to investigate differential activation of brain regions in the response inhibition network in children diagnosed with full or partial fetal alcohol syndrome (FAS/PFAS), compared with healthy controls. A rapid, event-related task with 120 Go and 60 NoGo trials was used to study children aged 8 to 12 years-8 with FAS/PFAS, 17 controls. Letters were projected sequentially, with Go and NoGo trials randomly interspersed across the task. BOLD signal in the whole brain was contrasted for the correct NoGo minus correct Go trials between the FAS/PFAS and control groups. Compared to the FAS/PFAS group, controls showed greater activation of the inferior frontal and anterior cingulate network linked to response inhibition in typically developing children. By contrast, the FAS/PFAS group showed greater BOLD response in dorsolateral prefrontal cortex and other middle prefrontal regions, suggesting compensation for inefficient function of pathways that normally mediate inhibitory processing. All group differences were significant after control for potential confounding variables. None of the effects of prenatal alcohol exposure on activation of the regions associated with response inhibition were attributable to the effects of this exposure on IQ. This is the first FASD GNG study in which all participants in the exposed group met criteria for a diagnosis of full FAS or PFAS. Although FASD is frequently comorbid with attention deficit hyperactivity disorder, the pattern of brain activation seen in these disorders differs, suggesting that different neural pathways mediate response inhibition in FASD and that different interventions for FASD are, therefore, warranted. Copyright © 2017 by the Research Society on Alcoholism.

The long-term effects of prenatal nicotine exposure on response inhibition: an fMRI study of young adults.

PubMed

Longo, Carmelinda A; Fried, Peter A; Cameron, Ian; Smith, Andra M

2013-01-01

The long-term effects of prenatal nicotine exposure on response inhibition were investigated in young adults using functional magnetic resonance imaging (fMRI). Participants were members of the Ottawa Prenatal Prospective Study, a longitudinal study that collected a unique body of information on participants from infancy to young adulthood, which allowed for the measurement of an unprecedented number of potentially confounding drug exposure variables including: prenatal marijuana and alcohol exposure and current marijuana, nicotine and alcohol use. Twelve young adults with prenatal nicotine exposure and 13 non-exposed controls performed a Go/No-Go task while fMRI blood oxygen level-dependent responses were examined. Despite similar task performance, participants prenatally exposed to nicotine demonstrated significantly greater activity in several regions of the brain that typically subserve response inhibition including the inferior frontal gyrus, the inferior parietal lobe, the thalamus and the basal ganglia. In addition, prenatally exposed participants showed greater activity in relatively large posterior regions of the cerebellum. These results suggest that prenatal nicotine exposure leads to altered neural functioning during response inhibition that continues into adulthood. This alteration is compensated for by recruitment of greater neural resources within regions of the brain that subserve response inhibition and the recruitment of additional brain regions to successfully perform the task. Response inhibition is an important executive functioning skill and impairments can impede functioning in much of everyday life. Thus, awareness of the continued long-term neural physiological effects of prenatal nicotine exposure is critical. Copyright © 2013 Elsevier Inc. All rights reserved.

Skeleton-based region competition for automated gray matter and white matter segmentation of human brain MR images

NASA Astrophysics Data System (ADS)

Chu, Yong; Chen, Ya-Fang; Su, Min-Ying; Nalcioglu, Orhan

2005-04-01

Image segmentation is an essential process for quantitative analysis. Segmentation of brain tissues in magnetic resonance (MR) images is very important for understanding the structural-functional relationship for various pathological conditions, such as dementia vs. normal brain aging. Different brain regions are responsible for certain functions and may have specific implication for diagnosis. Segmentation may facilitate the analysis of different brain regions to aid in early diagnosis. Region competition has been recently proposed as an effective method for image segmentation by minimizing a generalized Bayes/MDL criterion. However, it is sensitive to initial conditions - the "seeds", therefore an optimal choice of "seeds" is necessary for accurate segmentation. In this paper, we present a new skeleton-based region competition algorithm for automated gray and white matter segmentation. Skeletons can be considered as good "seed regions" since they provide the morphological a priori information, thus guarantee a correct initial condition. Intensity gradient information is also added to the global energy function to achieve a precise boundary localization. This algorithm was applied to perform gray and white matter segmentation using simulated MRI images from a realistic digital brain phantom. Nine different brain regions were manually outlined for evaluation of the performance in these separate regions. The results were compared to the gold-standard measure to calculate the true positive and true negative percentages. In general, this method worked well with a 96% accuracy, although the performance varied in different regions. We conclude that the skeleton-based region competition is an effective method for gray and white matter segmentation.

A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity

PubMed Central

Hilzendeger, Aline M.; Morgan, Donald A.; Brooks, Leonard; Dellsperger, David; Liu, Xuebo; Grobe, Justin L.; Rahmouni, Kamal; Sigmund, Curt D.

2012-01-01

The sympathetic nervous system, leptin, and renin-angiotensin system (RAS) have been implicated in obesity-associated hypertension. There is increasing evidence for the presence of both leptin and angiotensin II receptors in several key brain cardiovascular and metabolic control regions. We tested the hypothesis that the brain RAS plays a facilitatory role in the sympathetic nerve responses to leptin. In rats, intracerebroventricular (ICV) administration of losartan (5 μg) selectively inhibited increases in renal and brown adipose tissue (BAT) sympathetic nerve activity (SNA) produced by leptin (10 μg ICV) but did not reduce the SNA responses to corticotrophin-releasing factor (CRF) or the melanocortin receptor agonist MTII. In mice with deletion of angiotensin II type-1a receptors (AT1aR−/−), increases in renal and BAT SNA induced by leptin (2 μg ICV) were impaired whereas SNA responses to MTII were preserved. Decreases in food intake and body weight with ICV leptin did not differ in AT1aR−/− vs. AT1aR+/+ mice. ICV leptin in rats increased AT1aR and angiotensin-converting enzyme (ACE) mRNA in the subfornical organ and AT1aR mRNA in the arcuate nucleus, suggesting leptin-induced upregulation of the brain RAS in specific brain regions. To evaluate the role of de novo production of brain angiotensin II in SNA responses to leptin, we treated rats with captopril (12.5 μg ICV). Captopril attenuated leptin effects on renal and BAT SNA. In conclusion, these studies provide evidence that the brain RAS selectively facilitates renal and BAT sympathetic nerve responses to leptin while sparing effects on food intake. PMID:22610169

A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity.

PubMed

Hilzendeger, Aline M; Morgan, Donald A; Brooks, Leonard; Dellsperger, David; Liu, Xuebo; Grobe, Justin L; Rahmouni, Kamal; Sigmund, Curt D; Mark, Allyn L

2012-07-15

The sympathetic nervous system, leptin, and renin-angiotensin system (RAS) have been implicated in obesity-associated hypertension. There is increasing evidence for the presence of both leptin and angiotensin II receptors in several key brain cardiovascular and metabolic control regions. We tested the hypothesis that the brain RAS plays a facilitatory role in the sympathetic nerve responses to leptin. In rats, intracerebroventricular (ICV) administration of losartan (5 μg) selectively inhibited increases in renal and brown adipose tissue (BAT) sympathetic nerve activity (SNA) produced by leptin (10 μg ICV) but did not reduce the SNA responses to corticotrophin-releasing factor (CRF) or the melanocortin receptor agonist MTII. In mice with deletion of angiotensin II type-1a receptors (AT(1a)R(-/-)), increases in renal and BAT SNA induced by leptin (2 μg ICV) were impaired whereas SNA responses to MTII were preserved. Decreases in food intake and body weight with ICV leptin did not differ in AT(1a)R(-/-) vs. AT(1a)R(+/+) mice. ICV leptin in rats increased AT(1a)R and angiotensin-converting enzyme (ACE) mRNA in the subfornical organ and AT(1a)R mRNA in the arcuate nucleus, suggesting leptin-induced upregulation of the brain RAS in specific brain regions. To evaluate the role of de novo production of brain angiotensin II in SNA responses to leptin, we treated rats with captopril (12.5 μg ICV). Captopril attenuated leptin effects on renal and BAT SNA. In conclusion, these studies provide evidence that the brain RAS selectively facilitates renal and BAT sympathetic nerve responses to leptin while sparing effects on food intake.

4-dimensional functional profiling in the convulsant-treated larval zebrafish brain.

PubMed

Winter, Matthew J; Windell, Dylan; Metz, Jeremy; Matthews, Peter; Pinion, Joe; Brown, Jonathan T; Hetheridge, Malcolm J; Ball, Jonathan S; Owen, Stewart F; Redfern, Will S; Moger, Julian; Randall, Andrew D; Tyler, Charles R

2017-07-26

Functional neuroimaging, using genetically-encoded Ca 2+ sensors in larval zebrafish, offers a powerful combination of high spatiotemporal resolution and higher vertebrate relevance for quantitative neuropharmacological profiling. Here we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with light sheet microscopy and a novel image processing pipeline, for the 4D profiling of chemoconvulsant action in multiple brain regions. In untreated larvae, regions associated with autonomic functionality, sensory processing and stress-responsiveness, consistently exhibited elevated spontaneous activity. The application of drugs targeting different convulsant mechanisms (4-Aminopyridine, Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct spatiotemporal patterns of activity. These activity patterns showed some interesting parallels with what is known of the distribution of their respective molecular targets, but crucially also revealed system-wide neural circuit responses to stimulation or suppression. Drug concentration-response curves of neural activity were identified in a number of anatomically-defined zebrafish brain regions, and in vivo larval electrophysiology, also conducted in 4dpf larvae, provided additional measures of neural activity. Our quantification of network-wide chemoconvulsant drug activity in the whole zebrafish brain illustrates the power of this approach for neuropharmacological profiling in applications ranging from accelerating studies of drug safety and efficacy, to identifying pharmacologically-altered networks in zebrafish models of human neurological disorders.

The antidepressant venlafaxine disrupts brain monoamine levels and neuroendocrine responses to stress in rainbow trout.

PubMed

Melnyk-Lamont, Nataliya; Best, Carol; Gesto, Manuel; Vijayan, Mathilakath M

2014-11-18

Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is a widely prescribed antidepressant drug routinely detected in the aquatic environment. However, little is known about its impact on the physiology of nontarget organisms. We tested the hypothesis that venlafaxine perturbs brain monoamine levels and disrupts molecular responses essential for stress coping and feeding activity in fish. Rainbow trout (Oncorhynchus mykiss) were exposed to waterborne venlafaxine (0.2 and 1.0 μg/L) for 7 days. This treatment elevated norepinephrine, serotonin, and dopamine levels in the brain in a region-specific manner. Venlafaxine also increased the transcript levels of genes involved in stress and appetite regulation, including corticotropin releasing factor, pro-opiomelanocortin B, and glucose transporter type 2 in distinct brain regions of trout. The drug treatment reduced the total feed consumed per day, but did not affect the feeding behavior of the dominant and subordinate fish. However, the subordinate fish from the venlafaxine-exposed group had significantly higher plasma cortisol levels compared to the subordinate fish in the control group. Collectively, our results demonstrate that venlafaxine, at environmentally realistic levels, is a neuroendocrine disruptor, impacting the stress and feeding responses in rainbow trout. We propose the midbrain region as a key target for venlafaxine impact and the mode of action involves abnormal monoamine content in trout.

Activity in the human brain predicting differential heart rate responses to emotional facial expressions.

PubMed

Critchley, Hugo D; Rotshtein, Pia; Nagai, Yoko; O'Doherty, John; Mathias, Christopher J; Dolan, Raymond J

2005-02-01

The James-Lange theory of emotion proposes that automatically generated bodily reactions not only color subjective emotional experience of stimuli, but also necessitate a mechanism by which these bodily reactions are differentially generated to reflect stimulus quality. To examine this putative mechanism, we simultaneously measured brain activity and heart rate to identify regions where neural activity predicted the magnitude of heart rate responses to emotional facial expressions. Using a forewarned reaction time task, we showed that orienting heart rate acceleration to emotional face stimuli was modulated as a function of the emotion depicted. The magnitude of evoked heart rate increase, both across the stimulus set and within each emotion category, was predicted by level of activity within a matrix of interconnected brain regions, including amygdala, insula, anterior cingulate, and brainstem. We suggest that these regions provide a substrate for translating visual perception of emotional facial expression into differential cardiac responses and thereby represent an interface for selective generation of visceral reactions that contribute to the embodied component of emotional reaction.

Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission.

PubMed

Ragnarsson, Oskar; Stomby, Andreas; Dahlqvist, Per; Evang, Johan A; Ryberg, Mats; Olsson, Tommy; Bollerslev, Jens; Nyberg, Lars; Johannsson, Gudmundur

2017-08-01

Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 controls matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working-memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (p<0.001) and in the right inferior occipital gyrus (p<0.001) compared with controls. There was a trend towards lower functional brain responses in the left posterior hippocampus in patients (p=0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (p<0.001). During the working memory task, patients had lower response in the prefrontal cortices bilaterally (p<0.005). Patients, but not controls, had lower functional brain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Engaged listeners: shared neural processing of powerful political speeches

PubMed Central

Häcker, Frank E. K.; Honey, Christopher J.; Hasson, Uri

2015-01-01

Powerful speeches can captivate audiences, whereas weaker speeches fail to engage their listeners. What is happening in the brains of a captivated audience? Here, we assess audience-wide functional brain dynamics during listening to speeches of varying rhetorical quality. The speeches were given by German politicians and evaluated as rhetorically powerful or weak. Listening to each of the speeches induced similar neural response time courses, as measured by inter-subject correlation analysis, in widespread brain regions involved in spoken language processing. Crucially, alignment of the time course across listeners was stronger for rhetorically powerful speeches, especially for bilateral regions of the superior temporal gyri and medial prefrontal cortex. Thus, during powerful speeches, listeners as a group are more coupled to each other, suggesting that powerful speeches are more potent in taking control of the listeners’ brain responses. Weaker speeches were processed more heterogeneously, although they still prompted substantially correlated responses. These patterns of coupled neural responses bear resemblance to metaphors of resonance, which are often invoked in discussions of speech impact, and contribute to the literature on auditory attention under natural circumstances. Overall, this approach opens up possibilities for research on the neural mechanisms mediating the reception of entertaining or persuasive messages. PMID:25653012

Neuronal survival in the brain: neuron type-specific mechanisms.

PubMed

Pfisterer, Ulrich; Khodosevich, Konstantin

2017-03-02

Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation. Furthermore, pro-survival factors and intracellular responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro-survival constituents that might help them to adapt for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various types of immature neurons. Importantly, we mainly focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating data obtained in the PNS or spinal cord, and thus emphasize the influence of the complex brain environment on neuronal survival during development.

Maternal brain response to own baby-cry is affected by cesarean section delivery

PubMed Central

Swain, James E.; Tasgin, Esra; Mayes, Linda C.; Feldman, Ruth; Constable, R. Todd; Leckman, James F.

2011-01-01

A range of early circumstances surrounding the birth of a child affects peripartum hormones, parental behavior and infant wellbeing. One of these factors, which may lead to postpartum depression, is the mode of delivery: vaginal delivery (VD) or cesarean section delivery (CSD). To test the hypothesis that CSD mothers would be less responsive to own baby-cry stimuli than VD mothers in the immediate postpartum period, we conducted functional magnetic resonance imaging, 2–4 weeks after delivery, of the brains of six mothers who delivered vaginally and six who had an elective CSD. VD mothers’ brains were significantly more responsive than CSD mothers’ brains to their own baby-cry in the superior and middle temporal gyri, superior frontal gyrus, medial fusiform gyrus, superior parietal lobe, as well as regions of the caudate, thalamus, hypothalamus, amygdala and pons. Also, within preferentially active regions of VD brains, there were correlations across all 12 mothers with out-of-magnet variables. These include correlations between own baby-cry responses in the left and right lenticular nuclei and parental preoccupations (r = .64, p < .05 and .67, p < .05 respectively), as well as in the superior frontal cortex and Beck depression inventory (r = .78, p < .01). First this suggests that VD mothers are more sensitive to own baby-cry than CSD mothers in the early postpartum in sensory processing, empathy, arousal, motivation, reward and habit-regulation circuits. Second, independent of mode of delivery, parental worries and mood are related to specific brain activations in response to own baby-cry. PMID:18771508

Functional Characterization of the Human Speech Articulation Network.

PubMed

Basilakos, Alexandra; Smith, Kimberly G; Fillmore, Paul; Fridriksson, Julius; Fedorenko, Evelina

2018-05-01

A number of brain regions have been implicated in articulation, but their precise computations remain debated. Using functional magnetic resonance imaging, we examine the degree of functional specificity of articulation-responsive brain regions to constrain hypotheses about their contributions to speech production. We find that articulation-responsive regions (1) are sensitive to articulatory complexity, but (2) are largely nonoverlapping with nearby domain-general regions that support diverse goal-directed behaviors. Furthermore, premotor articulation regions show selectivity for speech production over some related tasks (respiration control), but not others (nonspeech oral-motor [NSO] movements). This overlap between speech and nonspeech movements concords with electrocorticographic evidence that these regions encode articulators and their states, and with patient evidence whereby articulatory deficits are often accompanied by oral-motor deficits. In contrast, the superior temporal regions show strong selectivity for articulation relative to nonspeech movements, suggesting that these regions play a specific role in speech planning/production. Finally, articulation-responsive portions of posterior inferior frontal gyrus show some selectivity for articulation, in line with the hypothesis that this region prepares an articulatory code that is passed to the premotor cortex. Taken together, these results inform the architecture of the human articulation system.

Is a Responsive Default Mode Network Required for Successful Working Memory Task Performance?

PubMed Central

Čeko, Marta; Gracely, John L.; Fitzcharles, Mary-Ann; Seminowicz, David A.; Schweinhardt, Petra

2015-01-01

In studies of cognitive processing using tasks with externally directed attention, regions showing increased (external-task-positive) and decreased or “negative” [default-mode network (DMN)] fMRI responses during task performance are dynamically responsive to increasing task difficulty. Responsiveness (modulation of fMRI signal by increasing load) has been linked directly to successful cognitive task performance in external-task-positive regions but not in DMN regions. To investigate whether a responsive DMN is required for successful cognitive performance, we compared healthy human subjects (n = 23) with individuals shown to have decreased DMN engagement (chronic pain patients, n = 28). Subjects performed a multilevel working-memory task (N-back) during fMRI. If a responsive DMN is required for successful performance, patients having reduced DMN responsiveness should show worsened performance; if performance is not reduced, their brains should show compensatory activation in external-task-positive regions or elsewhere. All subjects showed decreased accuracy and increased reaction times with increasing task level, with no significant group differences on either measure at any level. Patients had significantly reduced negative fMRI response (deactivation) of DMN regions (posterior cingulate/precuneus, medial prefrontal cortex). Controls showed expected modulation of DMN deactivation with increasing task difficulty. Patients showed significantly reduced modulation of DMN deactivation by task difficulty, despite their successful task performance. We found no evidence of compensatory neural recruitment in external-task-positive regions or elsewhere. Individual responsiveness of the external-task-positive ventrolateral prefrontal cortex, but not of DMN regions, correlated with task accuracy. These findings suggest that a responsive DMN may not be required for successful cognitive performance; a responsive external-task-positive network may be sufficient. SIGNIFICANCE STATEMENT We studied the relationship between responsiveness of the brain to increasing task demand and successful cognitive performance, using chronic pain patients as a probe. fMRI working memory studies show that two main cognitive networks [“external-task positive” and “default-mode network” (DMN)] are responsive to increasing task difficulty. The responsiveness of both of these brain networks is suggested to be required for successful task performance. The responsiveness of external-task-positive regions has been linked directly to successful cognitive task performance, as we also show here. However, pain patients show decreased engagement and responsiveness of the DMN but can perform a working memory task as well as healthy subjects, without demonstrable compensatory neural recruitment. Therefore, a responsive DMN might not be needed for successful cognitive performance. PMID:26290236

Is a Responsive Default Mode Network Required for Successful Working Memory Task Performance?

PubMed

Čeko, Marta; Gracely, John L; Fitzcharles, Mary-Ann; Seminowicz, David A; Schweinhardt, Petra; Bushnell, M Catherine

2015-08-19

In studies of cognitive processing using tasks with externally directed attention, regions showing increased (external-task-positive) and decreased or "negative" [default-mode network (DMN)] fMRI responses during task performance are dynamically responsive to increasing task difficulty. Responsiveness (modulation of fMRI signal by increasing load) has been linked directly to successful cognitive task performance in external-task-positive regions but not in DMN regions. To investigate whether a responsive DMN is required for successful cognitive performance, we compared healthy human subjects (n = 23) with individuals shown to have decreased DMN engagement (chronic pain patients, n = 28). Subjects performed a multilevel working-memory task (N-back) during fMRI. If a responsive DMN is required for successful performance, patients having reduced DMN responsiveness should show worsened performance; if performance is not reduced, their brains should show compensatory activation in external-task-positive regions or elsewhere. All subjects showed decreased accuracy and increased reaction times with increasing task level, with no significant group differences on either measure at any level. Patients had significantly reduced negative fMRI response (deactivation) of DMN regions (posterior cingulate/precuneus, medial prefrontal cortex). Controls showed expected modulation of DMN deactivation with increasing task difficulty. Patients showed significantly reduced modulation of DMN deactivation by task difficulty, despite their successful task performance. We found no evidence of compensatory neural recruitment in external-task-positive regions or elsewhere. Individual responsiveness of the external-task-positive ventrolateral prefrontal cortex, but not of DMN regions, correlated with task accuracy. These findings suggest that a responsive DMN may not be required for successful cognitive performance; a responsive external-task-positive network may be sufficient. We studied the relationship between responsiveness of the brain to increasing task demand and successful cognitive performance, using chronic pain patients as a probe. fMRI working memory studies show that two main cognitive networks ["external-task positive" and "default-mode network" (DMN)] are responsive to increasing task difficulty. The responsiveness of both of these brain networks is suggested to be required for successful task performance. The responsiveness of external-task-positive regions has been linked directly to successful cognitive task performance, as we also show here. However, pain patients show decreased engagement and responsiveness of the DMN but can perform a working memory task as well as healthy subjects, without demonstrable compensatory neural recruitment. Therefore, a responsive DMN might not be needed for successful cognitive performance. Copyright © 2015 the authors 0270-6474/15/3511596-11$15.00/0.

Changes in reward-induced brain activation in opiate addicts.

PubMed

Martin-Soelch, C; Chevalley, A F; Künig, G; Missimer, J; Magyar, S; Mino, A; Schultz, W; Leenders, K L

2001-10-01

Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with H(2)(15)O positron emission tomography (PET) during a visuo-spatial recognition task with delayed response in control subjects and in opiate addicts participating in a methadone program. Three conditions were defined by the types of feedback: nonsense feedback; nonmonetary reinforcement; or monetary reward, received by the subjects for a correct response. We found in the control subjects rCBF increases in regions associated with the meso-striatal and meso-corticolimbic circuits in response to both monetary reward and nonmonetary reinforcement. In opiate addicts, these regions were activated only in response to monetary reward. Furthermore, nonmonetary reinforcement elicited rCBF increases in limbic regions of the opiate addicts that were not activated in the control subjects. Because psychoactive drugs serve as rewards and directly affect regions of the dopaminergic system like the striatum, we conclude that the differences in rCBF increases between controls and addicts can be attributed to an adaptive consequence of the addiction process.

Fasting mediated increase in p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex of mice.

PubMed

Pitchaimani, Vigneshwaran; Arumugam, Somasundaram; Thandavarayan, Rajarajan Amirthalingam; Karuppagounder, Vengadeshprabhu; Sreedhar, Remya; Afrin, Rejina; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Nomoto, Mayumi; Sone, Hirohito; Suzuki, Kenji; Watanabe, Kenichi

2014-09-05

BAD-deficient mice and fasting have several common functional roles in seizures, beta-hydroxybutyrate (BHB) uptake in brain and alteration in counterregulatory hormonal regulation during hypoglycemia. Neuronal specific insulin receptor knockout (NIRKO) mice display impaired counterregulatory hormonal responses during hypoglycemia. In this study we investigated the fasting mediated expression of p-BAD(ser155) and p-AKT(ser473) in different regions of brain (prefrontal cortex, hippocampus, midbrain and hypothalamus). Fasting specifically increases p-BAD(ser155) and p-AKT(ser473) in prefrontal cortex and decreases in other regions of brain. Our results suggest that fasting may increase the uptake BHB by decreasing p-BAD(ser155) in the brain during hypoglycemia except prefrontal cortex and it uncovers specific functional area of p-BAD(ser155) and p-AKT(ser473) that may regulates counter regulatory hormonal response. Overall in support with previous findings, fasting mediated hypoglycemia activates prefrontal cortex insulin signaling which influences the hypothalamic paraventricular nucleus mediated activation of sympathoadrenal hormonal responses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Women's clitoris, vagina and cervix mapped on the sensory cortex: fMRI evidence

PubMed Central

Komisaruk, Barry R.; Wise, Nan; Frangos, Eleni; Liu, Wen-Ching; Allen, Kachina; Brody, Stuart

2011-01-01

Introduction The projection of vagina, uterine cervix, and nipple to the sensory cortex in humans has not been reported. Aims To map the sensory cortical fields of the clitoris, vagina, cervix and nipple, toward an elucidation of the neural systems underlying sexual response. Methods Using functional Magnetic Resonance Imaging (fMRI) we mapped sensory cortical responses to clitoral, vaginal, cervical, and nipple self-stimulation. For points of reference on the homunculus, we also mapped responses to the thumb and great toe (hallux) stimulation. Main Outcome Measures fMRI of brain regions activated by the various sensory stimuli. Results Clitoral, vaginal, and cervical self-stimulation activate differentiable sensory cortical regions, all clustered in the medial cortex (medial paracentral lobule). Nipple self-stimulation activated the genital sensory cortex (as well as the thoracic) region of the homuncular map. Conclusion The genital sensory cortex, identified in the classical Penfield homunculus based on electrical stimulation of the brain only in men, was confirmed for the first time in the literature by the present study in women, applying clitoral, vaginal, and cervical self-stimulation, and observing their regional brain responses using fMRI. Vaginal, clitoral, and cervical regions of activation were differentiable, consistent with innervation by different afferent nerves and different behavioral correlates. Activation of the genital sensory cortex by nipple self-stimulation was unexpected, but suggests a neurological basis for women’s reports of its erotogenic quality. PMID:21797981

Dissonance-Based Eating Disorder Prevention Program Reduces Reward Region Response to Thin Models; How Actions Shape Valuation

PubMed Central

Stice, Eric; Yokum, Sonja; Waters, Allison

2015-01-01

Research supports the effectiveness of a dissonance-based eating disorder prevention program wherein high-risk young women with body dissatisfaction critique the thin ideal, which reduces pursuit of this ideal, and the theory that dissonance induction contributes to these effects. Based on evidence that dissonance produces attitudinal change by altering neural representation of valuation, we tested whether completing the Body Project would reduce response of brain regions implicated in reward valuation to thin models. Young women with body dissatisfaction were randomized to this intervention or an educational control condition, completing assessments and fMRI scans while viewing images of thin versus average-weight female models at pre and post. Whole brain analyses indicated that, compared to controls, Body Project participants showed greater reductions in caudate response to images of thin versus average-weight models, though participants in the two conditions showed pretest differences in responsivity of other brain regions that might have contributed to this effect. Greater pre-post reductions in caudate and putamen response to thin models correlated with greater reductions in body dissatisfaction. The finding that the Body Project reduces caudate response to thin models provides novel preliminary evidence that this intervention reduces valuation of media images thought to contribute to body dissatisfaction and eating disorders, providing support for the intervention theory by documenting that this intervention alters an objective biological outcome. PMID:26641854

Dissonance-Based Eating Disorder Prevention Program Reduces Reward Region Response to Thin Models; How Actions Shape Valuation.

PubMed

Stice, Eric; Yokum, Sonja; Waters, Allison

2015-01-01

Research supports the effectiveness of a dissonance-based eating disorder prevention program wherein high-risk young women with body dissatisfaction critique the thin ideal, which reduces pursuit of this ideal, and the theory that dissonance induction contributes to these effects. Based on evidence that dissonance produces attitudinal change by altering neural representation of valuation, we tested whether completing the Body Project would reduce response of brain regions implicated in reward valuation to thin models. Young women with body dissatisfaction were randomized to this intervention or an educational control condition, completing assessments and fMRI scans while viewing images of thin versus average-weight female models at pre and post. Whole brain analyses indicated that, compared to controls, Body Project participants showed greater reductions in caudate response to images of thin versus average-weight models, though participants in the two conditions showed pretest differences in responsivity of other brain regions that might have contributed to this effect. Greater pre-post reductions in caudate and putamen response to thin models correlated with greater reductions in body dissatisfaction. The finding that the Body Project reduces caudate response to thin models provides novel preliminary evidence that this intervention reduces valuation of media images thought to contribute to body dissatisfaction and eating disorders, providing support for the intervention theory by documenting that this intervention alters an objective biological outcome.

Functional Imaging and Migraine: New Connections?

PubMed Central

Schwedt, Todd J.; Chong, Catherine D.

2015-01-01

Purpose of Review Over the last several years, a growing number of brain functional imaging studies have provided insights into mechanisms underlying migraine. This manuscript reviews the recent migraine functional neuroimaging literature and provides recommendations for future studies that will help fill knowledge gaps. Recent Findings Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies have identified brain regions that might be responsible for mediating the onset of a migraine attack and those associated with migraine symptoms. Enhanced activation of brain regions that facilitate processing of sensory stimuli suggests a mechanism by which migraineurs are hypersensitive to visual, olfactory, and cutaneous stimuli. Resting state functional connectivity MRI studies have identified numerous brain regions and functional networks with atypical functional connectivity in migraineurs, suggesting that migraine is associated with aberrant brain functional organization. Summary fMRI and PET studies that have identified brain regions and brain networks that are atypical in migraine have helped to describe the neurofunctional basis for migraine symptoms. Future studies should compare functional imaging findings in migraine to other headache and pain disorders and should explore the utility of functional imaging data as biomarkers for diagnostic and treatment purposes. PMID:25887764

Wavelet analysis of head acceleration response under dirac excitation for early oedema detection.

PubMed

Kostopoulos, V; Loutas, T H; Derdas, C; Douzinas, E

2008-04-01

The present work deals with the application of an innovative in-house developed wavelet-based methodology for the analysis of the acceleration responses of a human head complex model as a simulated diffused oedema progresses. The human head complex has been modeled as a structure consisting of three confocal prolate spheroids, whereas the three defined regions by the system of spheroids, from the outside to the inside, represent the scull, the region of cerebrospinal fluid, and the brain tissue. A Dirac-like pulse has been used to excite the human head complex model and the acceleration response of the system has been calculated and analyzed via the wavelet-based methodology. For the purpose of the present analysis, a wave propagation commercial finite element code, LS-DYNA 3D, has been used. The progressive diffused oedema was modeled via consecutive increases in brain volume accompanied by a decrease in brain density. It was shown that even a small increase in brain volume (at the level of 0.5%) can be identified by the effect it has on the vibration characteristics of the human head complex. More precisely, it was found that for some of the wavelet decomposition levels, the energy content changes monotonically as the brain volume increases, thus providing a useful index of monitoring an oncoming brain oedema before any brain damage appears due to uncontrolled intracranial hypertension. For the purpose of the present work and for the levels of brain volume increase considered in the present analysis, no pressure increase was assumed into the cranial vault and, associatively, no brain compliance variation.

Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain.

PubMed

Gerlofs-Nijland, Miriam E; van Berlo, Damien; Cassee, Flemming R; Schins, Roel P F; Wang, Kate; Campbell, Arezoo

2010-05-17

The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM), present in air pollution, and enhancement of central nervous system proinflammatory markers. In the present study, the association between exposure to air pollution (AP), derived from a specific source (diesel engine), and neuroinflammation was investigated. To elucidate whether specific regions of the brain are more susceptible to exposure to diesel-derived AP, various loci of the brain were separately analyzed. Rats were exposed for 6 hrs a day, 5 days a week, for 4 weeks to diesel engine exhaust (DEE) using a nose-only exposure chamber. The day after the final exposure, the brain was dissected into the following regions: cerebellum, frontal cortex, hippocampus, olfactory bulb and tubercles, and the striatum. Baseline levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 alpha (IL-1alpha) were dependent on the region analyzed and increased in the striatum after exposure to DEE. In addition, baseline level of activation of the transcription factors (NF-kappaB) and (AP-1) was also region dependent but the levels were not significantly altered after exposure to DEE. A similar, though not significant, trend was seen with the mRNA expression levels of TNF-alpha and TNF Receptor-subtype I (TNF-RI). Our results indicate that different brain regions may be uniquely responsive to changes induced by exposure to DEE. This study once more underscores the role of neuroinflammation in response to ambient air pollution, however, it is valuable to assess if and to what extent the observed changes may impact the normal function and cellular integrity of unique brain regions.

Central gene expression changes associated with enhanced neuroendocrine and autonomic response habituation to repeated noise stress after voluntary wheel running in rats

PubMed Central

Sasse, Sarah K.; Nyhuis, Tara J.; Masini, Cher V.; Day, Heidi E. W.; Campeau, Serge

2013-01-01

Accumulating evidence indicates that regular physical exercise benefits health in part by counteracting some of the negative physiological impacts of stress. While some studies identified reductions in some measures of acute stress responses with prior exercise, limited data were available concerning effects on cardiovascular function, and reported effects on hypothalamic-pituitary-adrenocortical (HPA) axis responses were largely inconsistent. Given that exposure to repeated or prolonged stress is strongly implicated in the precipitation and exacerbation of illness, we proposed the novel hypothesis that physical exercise might facilitate adaptation to repeated stress, and subsequently demonstrated significant enhancement of both HPA axis (glucocorticoid) and cardiovascular (tachycardia) response habituation to repeated noise stress in rats with long-term access to running wheels compared to sedentary controls. Stress habituation has been attributed to modifications of brain circuits, but the specific sites of adaptation and the molecular changes driving its expression remain unclear. Here, in situ hybridization histochemistry was used to examine regulation of select stress-associated signaling systems in brain regions representing likely candidates to underlie exercise-enhanced stress habituation. Analyzed brains were collected from active (6 weeks of wheel running) and sedentary rats following control, acute, or repeated noise exposures that induced a significantly faster rate of glucocorticoid response habituation in active animals but preserved acute noise responsiveness. Nearly identical experimental manipulations also induce a faster rate of cardiovascular response habituation in exercised, repeatedly stressed rats. The observed regulation of the corticotropin-releasing factor and brain-derived neurotrophic factor systems across several brain regions suggests widespread effects of voluntary exercise on central functions and related adaptations to stress across multiple response modalities. PMID:24324441

Social inclusion enhances biological motion processing: A functional near-infrared spectroscopy study

PubMed Central

Bolling, Danielle Z.; Pelphrey, Kevin A.; Kaiser, Martha D.

2012-01-01

Humans are especially tuned to the movements of other people. Neural correlates of this social attunement have been proposed to lie in and around the right posterior superior temporal sulcus (STS) region, which robustly responds to biological motion in contrast to a variety of non-biological motions. This response persists even when no form information is provided, as in point-light displays (PLDs). The aim of the current study was to assess the ability of functional near-infrared spectroscopy (fNIRS) to reliably measure brain responses to PLDs of biological motion, and determine the sensitivity of these responses to interpersonal contextual factors. To establish reliability, we measured brain activation to biological motion with fNIRS and functional magnetic resonance imaging (fMRI) during two separate sessions in an identical group of 12 participants. To establish sensitivity, brain responses to biological motion measured with fNIRS were subjected to an additional social manipulation where participants were either socially included or excluded before viewing PLDs of biological motion. Results revealed comparable brain responses to biological motion using fMRI and fNIRS in the right supramarginal gyrus. Further, social inclusion increased brain responses to biological motion in right supramarginal gyrus and posterior STS. Thus, fNIRS can reliably measure brain responses to biological motion and can detect social experience-dependent modulations of these brain responses. PMID:22941501

Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes.

PubMed

Renier, Nicolas; Adams, Eliza L; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E; Kadiri, Lolahon; Umadevi Venkataraju, Kannan; Zhou, Yu; Wang, Victoria X; Tang, Cheuk Y; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

2016-06-16

Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Last, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. Copyright © 2016 Elsevier Inc. All rights reserved.

Mapping of brain activity by automated volume analysis of immediate early genes

PubMed Central

Renier, Nicolas; Adams, Eliza L.; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E.; Kadiri, Lolahon; Venkataraju, Kannan Umadevi; Zhou, Yu; Wang, Victoria X.; Tang, Cheuk Y.; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

2016-01-01

Summary Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization and quantification of the activity of all neurons across the entire brain, which has not to date been achieved in the mammalian brain. We introduce a pipeline for high speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to Haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Lastly, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. PMID:27238021

The first taste is always with the eyes: a meta-analysis on the neural correlates of processing visual food cues.

PubMed

van der Laan, L N; de Ridder, D T D; Viergever, M A; Smeets, P A M

2011-03-01

Food selection is primarily guided by the visual system. Multiple functional neuro-imaging studies have examined the brain responses to visual food stimuli. However, the results of these studies are heterogeneous and there still is uncertainty about the core brain regions involved in the neural processing of viewing food pictures. The aims of the present study were to determine the concurrence in the brain regions activated in response to viewing pictures of food and to assess the modulating effects of hunger state and the food's energy content. We performed three Activation Likelihood Estimation (ALE) meta-analyses on data from healthy normal weight subjects in which we examined: 1) the contrast between viewing food and nonfood pictures (17 studies, 189 foci), 2) the modulation by hunger state (five studies, 48 foci) and 3) the modulation by energy content (seven studies, 86 foci). The most concurrent brain regions activated in response to viewing food pictures, both in terms of ALE values and the number of contributing experiments, were the bilateral posterior fusiform gyrus, the left lateral orbitofrontal cortex (OFC) and the left middle insula. Hunger modulated the response to food pictures in the right amygdala and left lateral OFC, and energy content modulated the response in the hypothalamus/ventral striatum. Overall, the concurrence between studies was moderate: at best 41% of the experiments contributed to the clusters for the contrast between food and nonfood. Therefore, future research should further elucidate the separate effects of methodological and physiological factors on between-study variations. Copyright © 2010 Elsevier Inc. All rights reserved.

Cerebral Apolipoprotein-D Is Hypoglycosylated Compared to Peripheral Tissues and Is Variably Expressed in Mouse and Human Brain Regions.

PubMed

Li, Hongyun; Ruberu, Kalani; Karl, Tim; Garner, Brett

2016-01-01

Recent studies have shown that cerebral apoD levels increase with age and in Alzheimer's disease (AD). In addition, loss of cerebral apoD in the mouse increases sensitivity to lipid peroxidation and accelerates AD pathology. Very little data are available, however, regarding the expression of apoD protein levels in different brain regions. This is important as both brain lipid peroxidation and neurodegeneration occur in a region-specific manner. Here we addressed this using western blotting of seven different regions (olfactory bulb, hippocampus, frontal cortex, striatum, cerebellum, thalamus and brain stem) of the mouse brain. Our data indicate that compared to most brain regions, the hippocampus is deficient in apoD. In comparison to other major organs and tissues (liver, spleen, kidney, adrenal gland, heart and skeletal muscle), brain apoD was approximately 10-fold higher (corrected for total protein levels). Our analysis also revealed that brain apoD was present at a lower apparent molecular weight than tissue and plasma apoD. Utilising peptide N-glycosidase-F and neuraminidase to remove N-glycans and sialic acids, respectively, we found that N-glycan composition (but not sialylation alone) were responsible for this reduction in molecular weight. We extended the studies to an analysis of human brain regions (hippocampus, frontal cortex, temporal cortex and cerebellum) where we found that the hippocampus had the lowest levels of apoD. We also confirmed that human brain apoD was present at a lower molecular weight than in plasma. In conclusion, we demonstrate apoD protein levels are variable across different brain regions, that apoD levels are much higher in the brain compared to other tissues and organs, and that cerebral apoD has a lower molecular weight than peripheral apoD; a phenomenon that is due to the N-glycan content of the protein.

Caloric Deprivation Increases Responsivity of Attention and Reward Brain Regions to Intake, Anticipated Intake, and Images of Palatable Foods

PubMed Central

Stice, Eric; Burger, Kyle; Yokum, Sonja

2013-01-01

Dietary restraint theoretically increases risk for binge eating, but prospective and experimental studies have produced contradictory findings, apparently because dietary restraint scales do not identify individuals who are reducing caloric intake. Yet, experimentally manipulated caloric deprivation increases responsivity of brain regions implicated in attention and reward to food images, which may contribute to binge eating. We tested whether self-imposed acute and longer-term caloric restriction increases responsivity of attention and reward regions to images, anticipated receipt, and receipt of palatable food using functional magnetic resonance imaging among female and male adolescents (Study 1 N = 34; Study 2 N = 51/81). Duration of acute caloric deprivation correlated positively with activation in regions implicated in attention, reward, and motivation in response to images, anticipated receipt, and receipt of palatable food (e.g., anterior cingulate cortex, orbitofrontal cortex, putamen, and precentral gyrus respectively). Youth in a longer-term negative energy balance likewise showed greater activation in attention (anterior cingulate cortex, ventral medial prefrontal cortex), visual processing (superior visual cortex), reward (caudate) and memory (hippocampus) regions in response to receipt and anticipated receipt of palatable food relative to those in neutral or positive energy balance. Results confirm that self-imposed caloric deprivation increases responsivity of attention, reward, and motivation regions to food, which may explain why caloric deprivation weight loss diets typically do not produce lasting weight loss. PMID:23201365

Chronic stress exposure may affect the brain's response to high calorie food cues and predispose to obesogenic eating habits.

PubMed

Tryon, Matthew S; Carter, Cameron S; Decant, Rashel; Laugero, Kevin D

2013-08-15

Exaggerated reactivity to food cues involving calorically-dense foods may significantly contribute to food consumption beyond caloric need. Chronic stress, which can induce palatable "comfort" food consumption, may trigger or reinforce neural pathways leading to stronger reactions to highly rewarding foods. We implemented functional magnetic resonance imaging (fMRI) to assess whether chronic stress influences activation in reward, motivation and executive brain regions in response to pictures of high calorie and low calorie foods in thirty women. On separate lab visits, we also assessed food intake from a snack food buffet and circulating cortisol. In women reporting higher chronic stress (HCS), pictures of high calorie foods elicited exaggerated activity in regions of the brain involving reward, motivation, and habitual decision-making. In response to pictures of high calorie food, higher chronic stress was also associated with significant deactivation in frontal regions (BA10; BA46) linked to strategic planning and emotional control. In functional connectivity analysis, HCS strengthened connectivity between amygdala and the putamen, while LCS enhanced connectivity between amygdala and the anterior cingulate and anterior prefrontal cortex (BA10). A hypocortisolemic signature and more consumption of high calorie foods from the snack buffet were observed in the HCS group. These results suggest that persistent stress exposure may alter the brain's response to food in ways that predispose individuals to poor eating habits which, if sustained, may increase risk for obesity. © 2013.

A preliminary study of the effects of working memory training on brain function in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Stevens, Michael C.; Gaynor, Alexandra; Bessette, Katie L.; Pearlson, Godfrey D.

2015-01-01

Working memory (WM) training improves WM ability in Attention-Deficit/Hyperactivity Disorder (ADHD), but its efficacy for non-cognitive ADHD impairments ADHD has been sharply debated. The purpose of this preliminary study was to characterize WM training-related changes in ADHD brain function and see if they were linked to clinical improvement. We examined 18 adolescents diagnosed with DSM-IV Combined-subtype ADHD before and after 25 sessions of WM training using a frequently employed approach (CogmedTM) using a nonverbal Sternberg WM fMRI task, neuropsychological tests, and participant- and parent-reports of ADHD symptom severity and associated functional impairment. Whole brain SPM8 analyses identified ADHD activation deficits compared to 18 non-ADHD control participants, then tested whether impaired ADHD frontoparietal brain activation would increase following WM training. Post hoc tests examined the relationships between neural changes and neurocognitive or clinical improvements. As predicted, WM training increased WM performance, ADHD clinical functioning, and WM-related ADHD brain activity in several frontal, parietal and temporal lobe regions. Increased left inferior frontal sulcus region activity was seen in all Encoding, Maintenance, and Retrieval Sternberg task phases. ADHD symptom severity improvements were most often positively correlated with activation gains in brain regions known to be engaged for WM-related executive processing; improvement of different symptom types had different neural correlates. The responsiveness of both amodal WM frontoparietal circuits and executive process-specific WM brain regions was altered by WM training. The latter might represent a promising, relatively unexplored treatment target for researchers seeking to optimize clinical response in ongoing ADHD WM training development efforts. PMID:26138580

Brain responses to vestibular pain and its anticipation in women with Genito-Pelvic Pain/Penetration Disorder.

PubMed

Pazmany, Els; Ly, Huynh Giao; Aerts, Leen; Kano, Michiko; Bergeron, Sophie; Verhaeghe, Johan; Peeters, Ronald; Tack, Jan; Dupont, Patrick; Enzlin, Paul; Van Oudenhove, Lukas

2017-01-01

In DSM-5, pain-related fear during anticipation of vaginal penetration is a diagnostic criterion of Genito-Pelvic Pain/Penetration Disorder (GPPPD). We aimed to investigate subjective and brain responses during anticipatory fear and subsequent induction of vestibular pain in women with GPPPD. Women with GPPPD (n = 18) and age-matched healthy controls (HC) (n = 15) underwent fMRI scanning during vestibular pain induction at individually titrated pain threshold after a cued anticipation period. (Pain-related) fear and anxiety traits were measured with questionnaires prior to scanning, and anticipatory fear and pain intensity were rated during scanning using visual analog scales. Women with GPPPD reported significantly higher levels of anticipatory fear and pain intensity. During anticipation and pain induction they had stronger and more extensive brain responses in regions involved in cognitive and affective aspects of pain perception, but the group difference did not reach significance for the anticipation condition. Pain-related fear and anxiety traits as well as anticipatory fear ratings were positively associated with pain ratings in GPPPD, but not in HC. Further, in HC, a negative association was found between anticipatory fear ratings and brain responses in regions involved in cognitive and affective aspects of pain perception, but not in women with GPPPD. Women with GPPPD are characterized by increased subjective and brain responses to vestibular pain and, to a lesser extent, its anticipation, with fear and anxiety associated with responses to pain, supporting the introduction of anticipatory fear as a criterion of GPPPD in DSM-5.

Brain discriminative cognition on the perception of touching different fabric using fingers actively.

PubMed

Wang, Q; Yu, W; Chen, K; Zhang, Z

2016-02-01

Using touching movement of fingers, human subjects can discriminate various tactile perception of fabric. As a continuation of the previous study, we aim to further investigate the discriminative mechanisms of the brain cognition to tactile stimulation of different fabric. We used functional magnetic resonance imaging to observe the brain responses when the subjects touched linen fabric, as well as revisited the data from the previous silk fabric. And all the subjects were asked to compare the perception of touching the two fabric. Combining the results of brain responses and perception comparison, we found that activation in the primary somatosensory cortex (SI) and the secondary somatosensory cortex (SII), especially parietal operculum 1 (OP1) in this region, could discriminate this two kinds of fabric distinctly. It is suggested that the functional regions involved in the macrogeometric properties of fabric (such as pliability) is in SI, and the perception of microgeometry of fabric surface (such as roughness and glutinousness) in SII, especially in the sub-region OP1 of the OP. Besides, activation in motor cortex can be a reference for the characterization of the brain cognition on the tactile stimulation of fabric. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neural Bases Of Food Perception: Coordinate-Based Meta-Analyses Of Neuroimaging Studies In Multiple Modalities

PubMed Central

Huerta, Claudia I; Sarkar, Pooja R; Duong, Timothy Q.; Laird, Angela R; Fox, Peter T

2013-01-01

Objective The purpose of this study was to compare the results of the three food-cue paradigms most commonly used for functional neuroimaging studies to determine: i) commonalities and differences in the neural response patterns by paradigm; and, ii) the relative robustness and reliability of responses to each paradigm. Design and Methods functional magnetic resonance imaging (fMRI) studies using standardized stereotactic coordinates to report brain responses to food cues were identified using on-line databases. Studies were grouped by food-cue modality as: i) tastes (8 studies); ii) odors (8 studies); and, iii) images (11 studies). Activation likelihood estimation (ALE) was used to identify statistically reliable regional responses within each stimulation paradigm. Results Brain response distributions were distinctly different for the three stimulation modalities, corresponding to known differences in location of the respective primary and associative cortices. Visual stimulation induced the most robust and extensive responses. The left anterior insula was the only brain region reliably responding to all three stimulus categories. Conclusions These findings suggest visual food-cue paradigm as promising candidate for imaging studies addressing the neural substrate of therapeutic interventions. PMID:24174404

The dynamics of error processing in the human brain as reflected by high-gamma activity in noninvasive and intracranial EEG.

PubMed

Völker, Martin; Fiederer, Lukas D J; Berberich, Sofie; Hammer, Jiří; Behncke, Joos; Kršek, Pavel; Tomášek, Martin; Marusič, Petr; Reinacher, Peter C; Coenen, Volker A; Helias, Moritz; Schulze-Bonhage, Andreas; Burgard, Wolfram; Ball, Tonio

2018-06-01

Error detection in motor behavior is a fundamental cognitive function heavily relying on local cortical information processing. Neural activity in the high-gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error-related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a multiscale picture of the global and local dynamics of error-related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error-related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error-related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error-related learning and behavioral adaptation. Our findings establish the basic spatio-temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error-related potential studies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Mood-dependent integration in discourse comprehension: happy and sad moods affect consistency processing via different brain networks.

PubMed

Egidi, Giovanna; Caramazza, Alfonso

2014-12-01

According to recent research on language comprehension, the semantic features of a text are not the only determinants of whether incoming information is understood as consistent. Listeners' pre-existing affective states play a crucial role as well. The current fMRI experiment examines the effects of happy and sad moods during comprehension of consistent and inconsistent story endings, focusing on brain regions previously linked to two integration processes: inconsistency detection, evident in stronger responses to inconsistent endings, and fluent processing (accumulation), evident in stronger responses to consistent endings. The analysis evaluated whether differences in the BOLD response for consistent and inconsistent story endings correlated with self-reported mood scores after a mood induction procedure. Mood strongly affected regions previously associated with inconsistency detection. Happy mood increased sensitivity to inconsistency in regions specific for inconsistency detection (e.g., left IFG, left STS), whereas sad mood increased sensitivity to inconsistency in regions less specific for language processing (e.g., right med FG, right SFG). Mood affected more weakly regions involved in accumulation of information. These results show that mood can influence activity in areas mediating well-defined language processes, and highlight that integration is the result of context-dependent mechanisms. The finding that language comprehension can involve different networks depending on people's mood highlights the brain's ability to reorganize its functions. Copyright © 2014 Elsevier Inc. All rights reserved.

Personality Is Reflected in the Brain's Intrinsic Functional Architecture

PubMed Central

Adelstein, Jonathan S.; Shehzad, Zarrar; Mennes, Maarten; DeYoung, Colin G.; Zuo, Xi-Nian; Kelly, Clare; Margulies, Daniel S.; Bloomfield, Aaron; Gray, Jeremy R.; Castellanos, F. Xavier; Milham, Michael P.

2011-01-01

Personality describes persistent human behavioral responses to broad classes of environmental stimuli. Investigating how personality traits are reflected in the brain's functional architecture is challenging, in part due to the difficulty of designing appropriate task probes. Resting-state functional connectivity (RSFC) can detect intrinsic activation patterns without relying on any specific task. Here we use RSFC to investigate the neural correlates of the five-factor personality domains. Based on seed regions placed within two cognitive and affective ‘hubs’ in the brain—the anterior cingulate and precuneus—each domain of personality predicted RSFC with a unique pattern of brain regions. These patterns corresponded with functional subdivisions responsible for cognitive and affective processing such as motivation, empathy and future-oriented thinking. Neuroticism and Extraversion, the two most widely studied of the five constructs, predicted connectivity between seed regions and the dorsomedial prefrontal cortex and lateral paralimbic regions, respectively. These areas are associated with emotional regulation, self-evaluation and reward, consistent with the trait qualities. Personality traits were mostly associated with functional connections that were inconsistently present across participants. This suggests that although a fundamental, core functional architecture is preserved across individuals, variable connections outside of that core encompass the inter-individual differences in personality that motivate diverse responses. PMID:22140453

Interpersonal violence in posttraumatic women: brain networks triggered by trauma-related pictures.

PubMed

Neumeister, Paula; Feldker, Katharina; Heitmann, Carina Y; Helmich, Ruth; Gathmann, Bettina; Becker, Michael P I; Straube, Thomas

2017-04-01

Interpersonal violence (IPV) is one of the most frequent causes for the development of posttraumatic stress disorder (PTSD) in women. Trauma-related triggers have been proposed to evoke automatic emotional responses in PTSD. The present functional magnetic resonance study investigated the neural basis of trauma-related picture processing in women with IPV-PTSD (n = 18) relative to healthy controls (n = 18) using a newly standardized trauma-related picture set and a non-emotional vigilance task. We aimed to identify brain activation and connectivity evoked by trauma-related pictures, and associations with PTSD symptom severity. We found hyperactivation during trauma-related vs neutral picture processing in both subcortical [basolateral amygdala (BLA), thalamus, brainstem] and cortical [anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), insula, occipital cortex] regions in IPV-PTSD. In patients, brain activation in amygdala, ACC, insula, occipital cortex and brainstem correlated positively with symptom severity. Furthermore, connectivity analyses revealed hyperconnectivity between BLA and dorsal ACC/mPFC. Results show symptom severity-dependent brain activation and hyperconnectivity in response to trauma-related pictures in brain regions related to fear and visual processing in women suffering from IPV-PTSD. These brain mechanisms appear to be associated with immediate responses to trauma-related triggers presented in a non-emotional context in this PTSD subgroup. © The Author (2016). Published by Oxford University Press.

Aberrant Spontaneous and Task-Dependent Functional Connections in the Anxious Brain

PubMed Central

MacNamara, Annmarie; DiGangi, Julia; Phan, K. Luan

2016-01-01

A number of brain regions have been implicated in the anxiety disorders, yet none of these regions in isolation has been distinguished as the sole or discrete site responsible for anxiety disorder pathology. Therefore, the identification of dysfunctional neural networks as represented by alterations in the temporal correlation of blood-oxygen level dependent (BOLD) signal across several brain regions in anxiety disorders has been increasingly pursued in the past decade. Here, we review task-independent (e.g., resting state) and task-induced functional connectivity magnetic resonance imaging (fcMRI) studies in the adult anxiety disorders (including trauma- and stressor-related and obsessive compulsive disorders). The results of this review suggest that anxiety disorder pathophysiology involves aberrant connectivity between amygdala-frontal and frontal-striatal regions, as well as within and between canonical “intrinsic” brain networks - the default mode and salience networks, and that evidence of these aberrations may help inform findings of regional activation abnormalities observed in the anxiety disorders. Nonetheless, significant challenges remain, including the need to better understand mixed findings observed using different methods (e.g., resting state and task-based approaches); the need for more developmental work; the need to delineate disorder-specific and transdiagnostic fcMRI aberrations in the anxiety disorders; and the need to better understand the clinical significance of fcMRI abnormalities. In meeting these challenges, future work has the potential to elucidate aberrant neural networks as intermediate, brain-based phenotypes to predict disease onset and progression, refine diagnostic nosology, and ascertain treatment mechanisms and predictors of treatment response across anxiety, trauma-related and obsessive compulsive disorders. PMID:27141532

The functional integration of the anterior cingulate cortex during conflict processing.

PubMed

Fan, Jin; Hof, Patrick R; Guise, Kevin G; Fossella, John A; Posner, Michael I

2008-04-01

Although functional activation of the anterior cingulate cortex (ACC) related to conflict processing has been studied extensively, the functional integration of the subdivisions of the ACC and other brain regions during conditions of conflict is still unclear. In this study, participants performed a task designed to elicit conflict processing by using flanker interference on target response while they were scanned using event-related functional magnetic resonance imaging. The physiological response of several brain regions in terms of an interaction between conflict processing and activity of the anterior rostral cingulate zone (RCZa) of the ACC, and the effective connectivity between this zone and other regions were examined using psychophysiological interaction analysis and dynamic causal modeling, respectively. There was significant integration of the RCZa with the caudal cingulate zone (CCZ) of the ACC and other brain regions such as the lateral prefrontal, primary, and supplementary motor areas above and beyond the main effect of conflict and baseline connectivity. The intrinsic connectivity from the RCZa to the CCZ was modulated by the context of conflict. These findings suggest that conflict processing is associated with the effective contribution of the RCZa to the neuronal activity of CCZ, as well as other cortical regions.

Region-Specific Protein Abundance Changes in the Brain of MPTP-induced Parkinson’s Disease Mouse Model

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

Zhang, Xu; Zhou, Jianying; Chin, Mark H

2010-02-15

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 non-redundant proteins with at least two unique peptides per protein. The relative abundance changes in eachmore » analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with significant MPTP-induced changes across different brain regions. 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit significant abundance changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. One of the interesting proteins is ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF-β pathway, which exhibited altered abundances in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall picture of proteome changes underlying both nigrostriatal pathways and other brain regions potentially involved in MPTP-induced neurodegeneration. The observed molecular changes provide a valuable reference resource for future hypothesis-driven functional studies of PD.« less

Brain imaging of pain sensitization in patients with knee osteoarthritis.

PubMed

Pujol, Jesus; Martínez-Vilavella, Gerard; Llorente-Onaindia, Jone; Harrison, Ben J; López-Solà, Marina; López-Ruiz, Marina; Blanco-Hinojo, Laura; Benito, Pere; Deus, Joan; Monfort, Jordi

2017-09-01

A relevant aspect in osteoarthritic pain is neural sensitization. This phenomenon involves augmented responsiveness to painful stimulation and may entail a clinically worse prognosis. We used functional magnetic resonance imaging (fMRI) to study pain sensitization in patients with knee osteoarthritis. Sixty patients were recruited and pain sensitization was clinically defined on the basis of regional spreading of pain (spreading sensitization) and increased pain response to repeated stimulation (temporal summation). Functional magnetic resonance imaging testing involved assessing brain responses to both pressure and heat stimulation. Thirty-three patients (55%) showed regional pain spreading (simple sensitization) and 19 patients (32%) showed both regional spreading and temporal summation. Sensitized patients were more commonly women. Direct painful pressure stimulation of the joint (articular interline) robustly activated all of the neural elements typically involved in pain perception, but did not differentiate sensitized and nonsensitized patients. Painful pressure stimulation on the anterior tibial surface (sensitized site) evoked greater activation in sensitized patients in regions typically involved in pain and also beyond these regions, extending to the auditory, visual, and ventral sensorimotor cortices. Painful heat stimulation of the volar forearm did not discriminate the sensitization phenomenon. Results confirm the high prevalence of pain sensitization secondary to knee osteoarthritis. Relevantly, the sensitization phenomenon was associated with neural changes extending beyond strict pain-processing regions with enhancement of activity in general sensory, nonnociceptive brain areas. This effect is in contrast to the changes previously identified in primary pain sensitization in fibromyalgia patients presenting with a weakening of the general sensory integration.

Task relevance modulates the behavioural and neural effects of sensory predictions

PubMed Central

Friston, Karl J.; Nobre, Anna C.

2017-01-01

The brain is thought to generate internal predictions to optimize behaviour. However, it is unclear whether predictions signalling is an automatic brain function or depends on task demands. Here, we manipulated the spatial/temporal predictability of visual targets, and the relevance of spatial/temporal information provided by auditory cues. We used magnetoencephalography (MEG) to measure participants’ brain activity during task performance. Task relevance modulated the influence of predictions on behaviour: spatial/temporal predictability improved spatial/temporal discrimination accuracy, but not vice versa. To explain these effects, we used behavioural responses to estimate subjective predictions under an ideal-observer model. Model-based time-series of predictions and prediction errors (PEs) were associated with dissociable neural responses: predictions correlated with cue-induced beta-band activity in auditory regions and alpha-band activity in visual regions, while stimulus-bound PEs correlated with gamma-band activity in posterior regions. Crucially, task relevance modulated these spectral correlates, suggesting that current goals influence PE and prediction signalling. PMID:29206225

Appearance Matters: Neural Correlates of Food Choice and Packaging Aesthetics

PubMed Central

Van der Laan, Laura N.; De Ridder, Denise T. D.; Viergever, Max A.; Smeets, Paul A. M.

2012-01-01

Neuro-imaging holds great potential for predicting choice behavior from brain responses. In this study we used both traditional mass-univariate and state-of-the-art multivariate pattern analysis to establish which brain regions respond to preferred packages and to what extent neural activation patterns can predict realistic low-involvement consumer choices. More specifically, this was assessed in the context of package-induced binary food choices. Mass-univariate analyses showed that several regions, among which the bilateral striatum, were more strongly activated in response to preferred food packages. Food choices could be predicted with an accuracy of up to 61.2% by activation patterns in brain regions previously found to be involved in healthy food choices (superior frontal gyrus) and visual processing (middle occipital gyrus). In conclusion, this study shows that mass-univariate analysis can detect small package-induced differences in product preference and that MVPA can successfully predict realistic low-involvement consumer choices from functional MRI data. PMID:22848586

Alcohol-induced apoptosis of oligodendrocytes in the fetal macaque brain.

PubMed

Creeley, Catherine E; Dikranian, Krikor T; Johnson, Stephen A; Farber, Nuri B; Olney, John W

2013-06-12

In utero exposure of the fetal non-human primate (NHP) brain to alcohol on a single occasion during early or late third-trimester gestation triggers widespread acute apoptotic death of cells in both gray and white matter (WM) regions of the fetal brain. In a prior publication, we documented that the dying gray matter cells are neurons, and described the regional distribution and magnitude of this cell death response. Here, we present new findings regarding the magnitude, identity and maturational status of the dying WM cells in these alcohol-exposed fetal NHP brains. Our findings document that the dying WM cells belong to the oligodendrocyte (OL) lineage. OLs become vulnerable when they are just beginning to generate myelin basic protein in preparation for myelinating axons, and they remain vulnerable throughout later stages of myelination. We found no evidence linking astrocytes, microglia or OL progenitors to this WM cell death response. The mean density (profiles per mm3) of dying WM cells in alcohol-exposed brains was 12.7 times higher than the mean density of WM cells dying by natural apoptosis in drug-naive control brains. In utero exposure of the fetal NHP brain to alcohol on a single occasion triggers widespread acute apoptotic death of neurons (previous study) and of OLs (present study) throughout WM regions of the developing brain. The rate of OL apoptosis in alcohol-exposed brains was 12.7 times higher than the natural OL apoptosis rate. OLs become sensitive to the apoptogenic action of alcohol when they are just beginning to generate constituents of myelin in their cytoplasm, and they remain vulnerable throughout later stages of myelination. There is growing evidence for a similar apoptotic response of both neurons and OLs following exposure of the developing brain to anesthetic and anticonvulsant drugs. Collectively, this body of evidence raises important questions regarding the role that neuro and oligo apoptosis may play in the human condition known as fetal alcohol spectrum disorder (FASD), and also poses a question whether other apoptogenic drugs, although long considered safe for pediatric/obstetric use, may have the potential to cause iatrogenic FASD-like developmental disability syndromes.

A comparison of functional brain changes associated with surgical versus behavioral weight loss

PubMed Central

Bruce, Amanda S.; Bruce, Jared M.; Ness, Abigail R.; Lepping, Rebecca J.; Malley, Stephen; Hancock, Laura; Powell, Josh; Patrician, Trisha M.; Breslin, Florence J.; Martin, Laura E.; Donnelly, Joseph E.; Brooks, William M.; Savage, Cary R.

2013-01-01

Objective Few studies have examined brain changes in response to effective weight loss; none have compared different methods of weight-loss intervention. We compared functional brain changes associated with a behavioral weight loss intervention to those associated with bariatric surgery. Methods 15 obese participants were recruited prior to adjustable gastric banding surgery and 16 obese participants were recruited prior to a behavioral diet intervention. Groups were matched for demographics and amount of weight lost. fMRI scans (visual food motivation paradigm while hungry and following a meal) were conducted before, and 12 weeks after surgery/behavioral intervention. Results When compared to bariatric patients in the pre-meal analyses, behavioral dieters showed increased activation to food images in right medial PFC and left precuneus following weight loss. When compared to behavioral dieters, bariatric patients showed increased activation in in bilateral temporal cortex following the weight loss. Conclusions Behavioral dieters showed increased responses to food cues in medial PFC – a region associated with valuation and processing of self-referent information – when compared to bariatric patients. Bariatric patients showed increased responses to food cues in brain regions associated with higher level perception—when compared to behavioral dieters. The method of weight loss determines unique changes in brain function. PMID:24115765

Regional deficiencies in chaperone-mediated autophagy underlie α-synuclein aggregation and neurodegeneration

PubMed Central

Malkus, Kristen A.; Ischiropoulos, Harry

2012-01-01

In neurodegenerative diseases, it remains unclear why certain brain regions are selectively vulnerable to protein aggregation. In transgenic mice expressing human A53T α-synuclein, the brainstem and spinal cord develop the most prominent α-synuclein inclusions which correlate with age-dependent motor dysfunction. Herein we present the novel finding that this selective aggregation is in part dependent on the inability of chaperone-mediated autophagy (CMA) to effectively degrade α-synuclein in these brain regions. Lysosomal assays revealed that CMA activity was significantly decreased in aggregation-prone regions compared to the remainder of the brain. Previously, CMA activity has been shown to be proportional to levels of the CMA receptor Lamp-2a. Using antibodies, brain tissue from Lamp-2a null mice, enzymatic deglycosylation, and mass spectrometry, we identified Lamp2a as a novel 72 kDa glycoprotein in the mouse brain. Examination of Lamp-2a levels revealed differences in expression across brain regions. The brainstem and the spinal cord had a more than three-fold greater levels of Lamp-2a as compared to regions less vulnerable to aggregation and exhibited a selective upregulation of Lamp-2a during development of α-synuclein inclusions. Despite this dynamic response of Lamp-2a, the levels of substrates bound to the brain lysosomes as well as the rates of substrate uptake and degradation were not proportional to the levels of Lamp-2a. These regional differences in CMA activity and Lamp-2a expression were found in both non-transgenic mice as well as A53T α-syn mice. Therefore, these are inherent variations and not a transgene-specific effect. However, differences in CMA activity may render select brain regions vulnerable to homeostatic dysfunction in the presence of stressors such as overexpression of human A53T α-syn. Collectively, the data provide a potential mechanism to explain the dichotomy of vulnerability or resistance that underlies brain regions during aggregate formation in neurodegenerative disease. PMID:22426402

Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood Pressure Over 2 Years.

PubMed

Jennings, J Richard; Heim, Alicia F; Sheu, Lei K; Muldoon, Matthew F; Ryan, Christopher; Gach, H Michael; Schirda, Claudiu; Gianaros, Peter J

2017-12-01

Hypertension is a presumptive risk factor for premature cognitive decline. However, lowering blood pressure (BP) does not uniformly reverse cognitive decline, suggesting that high BP per se may not cause cognitive decline. We hypothesized that essential hypertension has initial effects on the brain that, over time, manifest as cognitive dysfunction in conjunction with both brain vascular abnormalities and systemic BP elevation. Accordingly, we tested whether neuropsychological function and brain blood flow responses to cognitive challenges among prehypertensive individuals would predict subsequent progression of BP. Midlife adults (n=154; mean age, 49; 45% men) with prehypertensive BP underwent neuropsychological testing and assessment of regional cerebral blood flow (rCBF) response to cognitive challenges. Neuropsychological performance measures were derived for verbal and logical memory (memory), executive function, working memory, mental efficiency, and attention. A pseudo-continuous arterial spin labeling magnetic resonance imaging sequence compared rCBF responses with control and active phases of cognitive challenges. Brain areas previously associated with BP were grouped into composites for frontoparietal, frontostriatal, and insular-subcortical rCBF areas. Multiple regression models tested whether BP after 2 years was predicted by initial BP, initial neuropsychological scores, and initial rCBF responses to cognitive challenge. The neuropsychological composite of working memory (standardized beta, -0.276; se=0.116; P =0.02) and the frontostriatal rCBF response to cognitive challenge (standardized beta, 0.234; se=0.108; P =0.03) significantly predicted follow-up BP. Initial BP failed to significantly predict subsequent cognitive performance or rCBF. Changes in brain function may precede or co-occur with progression of BP toward hypertensive levels in midlife. © 2017 American Heart Association, Inc.

[Effects of noxious coldness and non-noxious warmth on the magnitude of cerebral cortex activation during intraoral stimulation with water].

PubMed

Xiuwen, Yang; Hongchen, Liu; Ke, Li; Zhen, Jin; Gang, Liu

2014-12-01

We used functional magnetic resonance imaging (fMRI) to explore the effects of noxious coldness and non-noxious warmth on the magnitude of cerebral cortex activation during intraoral stimulation with water. Six male and female subjects were subjected to whole-brain fMRI during the phasic delivery of non-noxious hot (23 °C) and no- xious cold (4 °C) water intraoral stimulation. A block-design blood oxygenation level-dependent fMRI scan covering the entire brain was also carried out. The activated cortical areas were as follows: left pre-/post-central gyrus, insula/operculum, anterior cingulate cortex (ACC), orbital frontal cortex (OFC), midbrain red nucleus, and thalamus. The activated cortical areas under cold condition were as follows: left occipital lobe, premotor cortex/Brodmann area (BA) 6, right motor language area BA44, lingual gyrus, parietal lobule (BA7, 40), and primary somatosensory cortex S I. Comparisons of the regional cerebral blood flow response magnitude were made among stereotactically concordant brain regions that showed significant responses under the two conditions of this study. Compared with non-noxious warmth, more regions were activated in noxious coldness, and the magnitude of activation in areas produced after non-noxious warm stimulation significantly increased. However, ACC only significantly increased the magnitude of activation under noxious coldness stimulation. Results suggested that a similar network of regions was activated common to the perception of pain and no-pain produced by either non-noxious warmth or noxious coldness stimulation. Non-noxious warmth also activated more brain regions and significantly increased the response magnitude of cerebral-cortex activation compared with noxious coldness. Noxious coldness stimulation further significantly increased the magnitude of activation in ACC areas compared with noxious warmth.

Exploring avian deep-brain photoreceptors and their role in activating the neuroendocrine regulation of gonadal development.

PubMed

Kuenzel, Wayne J; Kang, Seong W; Zhou, Z Jimmy

2015-04-01

In the eyes of mammals, specialized photoreceptors called intrinsically photosensitive retinal ganglion cells (ipRGC) have been identified that sense photoperiodic or daylight exposure, providing them over time with seasonal information. Detectors of photoperiods are critical in vertebrates, particularly for timing the onset of reproduction each year. In birds, the eyes do not appear to monitor photoperiodic information; rather, neurons within at least 4 different brain structures have been proposed to function in this capacity. Specialized neurons, called deep brain photoreceptors (DBP), have been found in the septum and 3 hypothalamic areas. Within each of the 4 brain loci, one or more of 3 unique photopigments, including melanopsin, neuropsin, and vertebrate ancient opsin, have been identified. An experiment was designed to characterize electrophysiological responses of neurons proposed to be avian DBP following light stimulation. A second study used immature chicks raised under short-day photoperiods and transferred to long day lengths. Gene expression of photopigments was then determined in 3 septal-hypothalamic regions. Preliminary electrophysiological data obtained from patch-clamping neurons in brain slices have shown that bipolar neurons in the lateral septal organ responded to photostimulation comparable with mammalian ipRGC, particularly by showing depolarization and a delayed, slow response to directed light stimulation. Utilizing real-time reverse-transcription PCR, it was found that all 3 photopigments showed significantly increased gene expression in the septal-hypothalamic regions in chicks on the third day after being transferred to long-day photoperiods. Each dissected region contained structures previously proposed to have DBP. The highly significant increased gene expression for all 3 photopigments on the third, long-day photoperiod in brain regions proposed to contain 4 structures with DBP suggests that all 3 types of DBP (melanopsin, neuropsin, and vertebrate ancient opsin) in more than one neural site in the septal-hypothalamic area are involved in reproductive function. The neural response to light of at least 2 of the proposed DBP in the septal/hypothalamic region resembles the primitive, functional, sensory ipRGC well characterized in mammals. ©2015 Poultry Science Association Inc.

Continuous functional magnetic resonance imaging reveals dynamic nonlinearities of "dose-response" curves for finger opposition.

PubMed

Berns, G S; Song, A W; Mao, H

1999-07-15

Linear experimental designs have dominated the field of functional neuroimaging, but although successful at mapping regions of relative brain activation, the technique assumes that both cognition and brain activation are linear processes. To test these assumptions, we performed a continuous functional magnetic resonance imaging (MRI) experiment of finger opposition. Subjects performed a visually paced bimanual finger-tapping task. The frequency of finger tapping was continuously varied between 1 and 5 Hz, without any rest blocks. After continuous acquisition of fMRI images, the task-related brain regions were identified with independent components analysis (ICA). When the time courses of the task-related components were plotted against tapping frequency, nonlinear "dose- response" curves were obtained for most subjects. Nonlinearities appeared in both the static and dynamic sense, with hysteresis being prominent in several subjects. The ICA decomposition also demonstrated the spatial dynamics with different components active at different times. These results suggest that the brain response to tapping frequency does not scale linearly, and that it is history-dependent even after accounting for the hemodynamic response function. This implies that finger tapping, as measured with fMRI, is a nonstationary process. When analyzed with a conventional general linear model, a strong correlation to tapping frequency was identified, but the spatiotemporal dynamics were not apparent.

Engaged listeners: shared neural processing of powerful political speeches.

PubMed

Schmälzle, Ralf; Häcker, Frank E K; Honey, Christopher J; Hasson, Uri

2015-08-01

Powerful speeches can captivate audiences, whereas weaker speeches fail to engage their listeners. What is happening in the brains of a captivated audience? Here, we assess audience-wide functional brain dynamics during listening to speeches of varying rhetorical quality. The speeches were given by German politicians and evaluated as rhetorically powerful or weak. Listening to each of the speeches induced similar neural response time courses, as measured by inter-subject correlation analysis, in widespread brain regions involved in spoken language processing. Crucially, alignment of the time course across listeners was stronger for rhetorically powerful speeches, especially for bilateral regions of the superior temporal gyri and medial prefrontal cortex. Thus, during powerful speeches, listeners as a group are more coupled to each other, suggesting that powerful speeches are more potent in taking control of the listeners' brain responses. Weaker speeches were processed more heterogeneously, although they still prompted substantially correlated responses. These patterns of coupled neural responses bear resemblance to metaphors of resonance, which are often invoked in discussions of speech impact, and contribute to the literature on auditory attention under natural circumstances. Overall, this approach opens up possibilities for research on the neural mechanisms mediating the reception of entertaining or persuasive messages. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

A critical review of 5-HT brain microdialysis and behavior.

PubMed

Rueter, L E; Fornal, C A; Jacobs, B L

1997-01-01

Serotonin (5-HT) has been implicated in many central nervous system-mediated functions including sleep, arousal, feeding, motor activity and the stress response. In order to help establish the precise role of 5-HT in physiology and behavior, in vivo microdialysis studies have sought to identify the conditions under which the release of 5-HT is altered. Extracellular 5-HT levels have been monitored in more than fifteen regions of the brain during a variety of spontaneous behaviors, and in response to several physiological, environmental, and behavioral manipulations. The vast majority of these studies found increases (30-100%) in 5-HT release in almost all brain regions studied. Since electrophysiological studies have shown that behavioral arousal is the primary determinant of brain serotonergic neuronal activity, we suggest that the increase in 5-HT release seen during a wide variety of experimental conditions is largely due to one factor, namely an increase in behavioral arousal/motor activity associated with the manipulation.

Artifact suppression and analysis of brain activities with electroencephalography signals.

PubMed

Rashed-Al-Mahfuz, Md; Islam, Md Rabiul; Hirose, Keikichi; Molla, Md Khademul Islam

2013-06-05

Brain-computer interface is a communication system that connects the brain with computer (or other devices) but is not dependent on the normal output of the brain (i.e., peripheral nerve and muscle). Electro-oculogram is a dominant artifact which has a significant negative influence on further analysis of real electroencephalography data. This paper presented a data adaptive technique for artifact suppression and brain wave extraction from electroencephalography signals to detect regional brain activities. Empirical mode decomposition based adaptive thresholding approach was employed here to suppress the electro-oculogram artifact. Fractional Gaussian noise was used to determine the threshold level derived from the analysis data without any training. The purified electroencephalography signal was composed of the brain waves also called rhythmic components which represent the brain activities. The rhythmic components were extracted from each electroencephalography channel using adaptive wiener filter with the original scale. The regional brain activities were mapped on the basis of the spatial distribution of rhythmic components, and the results showed that different regions of the brain are activated in response to different stimuli. This research analyzed the activities of a single rhythmic component, alpha with respect to different motor imaginations. The experimental results showed that the proposed method is very efficient in artifact suppression and identifying individual motor imagery based on the activities of alpha component.

Efficiency of weak brain connections support general cognitive functioning.

PubMed

Santarnecchi, Emiliano; Galli, Giulia; Polizzotto, Nicola Riccardo; Rossi, Alessandro; Rossi, Simone

2014-09-01

Brain network topology provides valuable information on healthy and pathological brain functioning. Novel approaches for brain network analysis have shown an association between topological properties and cognitive functioning. Under the assumption that "stronger is better", the exploration of brain properties has generally focused on the connectivity patterns of the most strongly correlated regions, whereas the role of weaker brain connections has remained obscure for years. Here, we assessed whether the different strength of connections between brain regions may explain individual differences in intelligence. We analyzed-functional connectivity at rest in ninety-eight healthy individuals of different age, and correlated several connectivity measures with full scale, verbal, and performance Intelligent Quotients (IQs). Our results showed that the variance in IQ levels was mostly explained by the distributed communication efficiency of brain networks built using moderately weak, long-distance connections, with only a smaller contribution of stronger connections. The variability in individual IQs was associated with the global efficiency of a pool of regions in the prefrontal lobes, hippocampus, temporal pole, and postcentral gyrus. These findings challenge the traditional view of a prominent role of strong functional brain connections in brain topology, and highlight the importance of both strong and weak connections in determining the functional architecture responsible for human intelligence variability. Copyright © 2014 Wiley Periodicals, Inc.

Normalization as a canonical neural computation

PubMed Central

Carandini, Matteo; Heeger, David J.

2012-01-01

There is increasing evidence that the brain relies on a set of canonical neural computations, repeating them across brain regions and modalities to apply similar operations to different problems. A promising candidate for such a computation is normalization, in which the responses of neurons are divided by a common factor that typically includes the summed activity of a pool of neurons. Normalization was developed to explain responses in the primary visual cortex and is now thought to operate throughout the visual system, and in many other sensory modalities and brain regions. Normalization may underlie operations such as the representation of odours, the modulatory effects of visual attention, the encoding of value and the integration of multisensory information. Its presence in such a diversity of neural systems in multiple species, from invertebrates to mammals, suggests that it serves as a canonical neural computation. PMID:22108672

Neurovascular Regulation in the Ischemic Brain

PubMed Central

Jackman, Katherine

2015-01-01

Abstract Significance: The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. Recent Advances and Critical Issues: The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active responses such as cerebral autoregulation, which acts to maintain constant cerebral blood flow in response to changing blood pressure, and functional hyperemia, which couples blood supply with synaptic activity, allow the brain to maintain adequate cerebral perfusion in the face of varying supply or demand. In the presence of stroke risk factors, such as hypertension and diabetes, these protective processes are impaired and the susceptibility of the brain to ischemic injury is increased. One potential mechanism for the increased injury is that collateral flow arising from the normally perfused brain and supplying blood flow to the ischemic region is suppressed, resulting in more severe ischemia. Future Directions: Approaches to support collateral flow may ameliorate the outcome of focal cerebral ischemia by rescuing cerebral perfusion in potentially viable regions of the ischemic territory. Antioxid. Redox Signal. 22, 149–160. PMID:24328757

Experiential, Autonomic, and Neural Responses During Threat Anticipation Vary as a Function of Threat Intensity and Neuroticism

PubMed Central

Drabant, Emily M; Kuo, Janice R; Ramel, Wiveka; Blechert, Jens; Edge, Michael D; Cooper, Jeff R; Goldin, Philippe R; Hariri, Ahmad R; Gross, James J

2011-01-01

Anticipatory emotional responses play a crucial role in preparing individuals for impending challenges. They do this by triggering a coordinated set of changes in behavioral, autonomic, and neural response systems. In the present study, we examined the biobehavioral impact of varying levels of anticipatory anxiety, using a shock anticipation task in which unpredictable electric shocks were threatened and delivered to the wrist at variable intervals and intensities (safe, medium, strong). This permitted investigation of a dynamic range of anticipatory anxiety responses. In two studies, 95 and 51 healthy female participants, respectively, underwent this shock anticipation task while providing continuous ratings of anxiety experience and electrodermal responding (Study 1) and during fMRI BOLD neuroimaging (Study 2). Results indicated a step-wise pattern of responding in anxiety experience and electrodermal responses. Several brain regions showed robust responses to shock anticipation relative to safe trials, including the hypothalamus, periaqueductal gray, caudate, precentral gyrus, thalamus, insula, ventrolateral PFC, dorsomedial PFC, and ACC. A subset of these regions demonstrated a linear pattern of increased responding from safe to medium to strong trials, including the bilateral insula, ACC, and inferior frontal gyrus. These responses were modulated by individual differences in neuroticism, such that those high in neuroticism showed exaggerated anxiety experience across the entire task, and reduced brain activation from medium to strong trials in a subset of brain regions. These findings suggest that individual differences in neuroticism may influence sensitivity to anticipatory threat and provide new insights into the mechanism through which neuroticism may confer risk for developing anxiety disorders via dysregulated anticipatory responses. PMID:21093595

fMRI study of neural sensitization to hedonic stimuli in long-term, daily cannabis users.

PubMed

Filbey, Francesca M; Dunlop, Joseph; Ketcherside, Ariel; Baine, Jessica; Rhinehardt, Tyler; Kuhn, Brittany; DeWitt, Sam; Alvi, Talha

2016-10-01

Although there is emergent evidence illustrating neural sensitivity to cannabis cues in cannabis users, the specificity of this effect to cannabis cues as opposed to a generalized hyper-sensitivity to hedonic stimuli has not yet been directly tested. Using fMRI, we presented 53 daily, long-term cannabis users and 68 non-using controls visual and tactile cues for cannabis, a natural reward, and, a sensory-perceptual control object to evaluate brain response to hedonic stimuli in cannabis users. The results showed an interaction between group and reward type such that the users had greater response during cannabis cues relative to natural reward cues (i.e., fruit) in the orbitofrontal cortex, striatum, anterior cingulate gyrus, and ventral tegmental area compared to non-users (cluster-threshold z = 2.3, P < 0.05). In the users, there were positive brain-behavior correlations between neural response to cannabis cues in fronto-striatal-temporal regions and subjective craving, marijuana-related problems, withdrawal symptoms, and levels of THC metabolites (cluster-threshold z = 2.3, P < 0.05). These findings demonstrate hyper-responsivity, and, specificity of brain response to cannabis cues in long-term cannabis users that are above that of response to natural reward cues. These observations are concordant with incentive sensitization models suggesting sensitization of mesocorticolimbic regions and disruption of natural reward processes following drug use. Although the cross-sectional nature of this study does not provide information on causality, the positive correlations between neural response and indicators of cannabis use (i.e., THC levels) suggest that alterations in the reward system are, in part, related to cannabis use. Hum Brain Mapp 37:3431-3443, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Longitudinal Growth Curves of Brain Function Underlying Inhibitory Control through Adolescence

PubMed Central

Foran, William; Velanova, Katerina; Luna, Beatriz

2013-01-01

Neuroimaging studies suggest that developmental improvements in inhibitory control are primarily supported by changes in prefrontal executive function. However, studies are contradictory with respect to how activation in prefrontal regions changes with age, and they have yet to analyze longitudinal data using growth curve modeling, which allows characterization of dynamic processes of developmental change, individual differences in growth trajectories, and variables that predict any interindividual variability in trajectories. In this study, we present growth curves modeled from longitudinal fMRI data collected over 302 visits (across ages 9 to 26 years) from 123 human participants. Brain regions within circuits known to support motor response control, executive control, and error processing (i.e., aspects of inhibitory control) were investigated. Findings revealed distinct developmental trajectories for regions within each circuit and indicated that a hierarchical pattern of maturation of brain activation supports the gradual emergence of adult-like inhibitory control. Mean growth curves of activation in motor response control regions revealed no changes with age, although interindividual variability decreased with development, indicating equifinality with maturity. Activation in certain executive control regions decreased with age until adolescence, and variability was stable across development. Error-processing activation in the dorsal anterior cingulate cortex showed continued increases into adulthood and no significant interindividual variability across development, and was uniquely associated with task performance. These findings provide evidence that continued maturation of error-processing abilities supports the protracted development of inhibitory control over adolescence, while motor response control regions provide early-maturing foundational capacities and suggest that some executive control regions may buttress immature networks as error processing continues to mature. PMID:24227721

Vocal parameters that indicate threat level correlate with FOS immunolabeling in social and vocal control brain regions.

PubMed

Ellis, Jesse M S; Riters, Lauren V

2012-01-01

Transmitting information via communicative signals is integral to interacting with conspecifics, and some species achieve this task by varying vocalizations to reflect context. Although signal variation is critical to social interactions, the underlying neural control has not been studied. In response to a predator, black-capped chickadees (Poecile atricapilla) produce mobbing calls (chick-a-dee calls) with various parameters, some of which convey information about the threat stimulus. We predicted that vocal parameters indicative of threat would be associated with distinct patterns of neuronal activity within brain areas involved in social behavior and those involved in the sensorimotor control of vocal production. To test this prediction, we measured the syntax and structural aspects of chick-a-dee call production in response to a hawk model and assessed the protein product of the immediate early gene FOS in brain regions implicated in context-specific vocal and social behavior. These regions include the medial preoptic area (POM) and lateral septum (LS), as well as regions involved in vocal motor control, including the dorsomedial nucleus of the intercollicular complex and the HVC. We found correlations linking call rate (previously demonstrated to reflect threat) to labeling in the POM and LS. Labeling in the HVC correlated with the number of D notes per call, which may also signal threat level. Labeling in the call control region dorsomedial nucleus was associated with the structure of D notes and the overall number of notes, but not call rate or type of notes produced. These results suggest that the POM and LS may influence attributes of vocalizations produced in response to predators and that the brain region implicated in song control, the HVC, also influences call production. Because variation in chick-a-dee call rate indicates predator threat, we speculate that these areas could integrate with motor control regions to imbue mobbing signals with additional information about threat level. Copyright © 2011 S. Karger AG, Basel.

Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.

PubMed

Nomi, Jason S; Bolt, Taylor S; Ezie, C E Chiemeka; Uddin, Lucina Q; Heller, Aaron S

2017-05-31

Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation. SIGNIFICANCE STATEMENT Although brain signal variability has traditionally been considered a source of unwanted noise, recent work demonstrates that variability in brain signals during task performance is related to brain maturation in old age as well as individual differences in behavioral performance. The current results demonstrate that intrinsic fluctuations in resting-state variability exhibit unique maturation trajectories in specific brain regions and systems, particularly those supporting salience detection. These results have implications for investigations of brain development and aging, as well as interpretations of brain function underlying behavioral changes across the lifespan. Copyright © 2017 the authors 0270-6474/17/375539-10$15.00/0.

The evolving neurobiology of gut feelings.

PubMed

Mayer, E A; Naliboff, B; Munakata, J

2000-01-01

The bi-directional communication between limbic regions and the viscera play a central role in the generation and expression of emotional responses and associated emotional feelings. The response of different viscera to distinct, emotion-specific patterns of autonomic output is fed back to the brain, in particular to the cingulofrontal convergence region. Even though this process unfolds largely without conscious awareness, it plays an important role in emotional function and may influence rational decision making in the healthy individual. Alterations in this bi-directional process such as peripheral pathologies within the gut or alterations at the brain level may explain the close association between certain affective disorders and functional visceral syndromes.

Changes in Regional Brain Homogeneity Induced by Electro-Acupuncture Stimulation at the Baihui Acupoint in Healthy Subjects: A Functional Magnetic Resonance Imaging Study.

PubMed

Deng, Demao; Duan, Gaoxiong; Liao, Hai; Liu, Yanfei; Wang, Geliang; Liu, Huimei; Tang, Lijun; Pang, Yong; Tao, Jien; He, Xin; Yuan, Wenzhao; Liu, Peng

2016-10-01

According to the Traditional Chinese Medicine theory of acupuncture, Baihui (GV20) is applied to treat neurological and psychiatric disorders. However, the relationships between neural responses and GV20 remain unknown. Thus, the main aim of this study was to examine the brain responses induced by electro-acupuncture stimulation (EAS) at GV20. Functional magnetic resonance imaging (fMRI) was performed in 33 healthy subjects. Based on the non-repeated event-related (NRER) paradigm, group differences were examined between GV20 and a sham acupoint using the regional homogeneity (ReHo) method. Compared with the sham acupoint, EAS at GV20 induced increased ReHo in regions including the orbital frontal cortex (OFC), middle cingulate cortex (MCC), precentral cortex, and precuneus (preCUN). Decreased ReHo was found in the anterior cingulate cortex (ACC), supplementary motor area (SMA), thalamus, putamen, and cerebellum. The current findings provide preliminary neuroimaging evidence to indicate that EAS at GV20 could induce a specific pattern of neural responses by analysis of ReHo of brain activity. These findings might improve the understanding of mechanisms of acupuncture stimulation at GV20.

Enhancing response inhibition by incentive: Comparison of adolescents with and without substance use disorder

PubMed Central

Chung, Tammy; Geier, Charles; Luna, Beatriz; Pajtek, Stefan; Terwilliger, Robert; Thatcher, Dawn; Clark, Duncan

2010-01-01

Effective response inhibition is a key component of recovery from addiction. Some research suggests that response inhibition can be enhanced through reward contingencies. We examined the effect of monetary incentive on response inhibition among adolescents with and without substance use disorder (SUD) using a fast event-related fMRI antisaccade reward task. The fMRI task permits investigation of how reward (monetary incentive) might modulate inhibitory control during three task phases: cue presentation (reward or neutral trial), response preparation, and response execution. Adolescents with lifetime SUD (n=12; 100% marijuana use disorder) were gender and age-matched to healthy controls (n=12). Monetary incentive facilitated inhibitory control for SUD adolescents; for healthy controls, the difference in error rate for neutral and reward trials was not significant. There were no significant differences in behavioral performance between groups across reward and neutral trials, however, group differences in regional brain activation were identified. During the response preparation phase of reward trials, SUD adolescents, compared to controls, showed increased activation of prefrontal and oculomotor control (e.g., frontal eye field) areas, brain regions that have been associated with effective response inhibition. Results indicate differences in brain activation between SUD and control youth when preparing to inhibit a prepotent response in the context of reward, and support a possible role for incentives in enhancing response inhibition among youth with SUD. PMID:21115229

Neural Correlates and Connectivity underlying Stress-related Impulse Control Difficulties in Alcoholism

PubMed Central

Seo, Dongju; Lacadie, Cheryl M.; Sinha, Rajita

2016-01-01

BACKGROUND Stress triggers impulsive and addictive behaviors, and alcoholism has been frequently associated with increased stress sensitivity and impulse control problems. However, neural correlates underlying the link between alcoholism and impulsivity in the context of stress in patients with alcohol use disorders (AUD) have not been well studied. METHOD The current study investigated neural correlates and connectivity patterns associated with impulse control difficulties in abstinent AUD patients. Using functional magnetic resonance imaging, brain responses of 37 AUD inpatients and 37 demographically-matched healthy controls were examined during brief individualized imagery trials of stress, alcohol-cue and neutral-relaxing conditions. Stress-related impulsivity was measured using a subscale score of impulse control problems from Difficulties in Emotion Regulation Scale (DERS). RESULTS Impulse control difficulties in AUD patients were significantly associated with hypoactive response to stress in the ventromedial prefrontal cortex (VmPFC), right caudate, and left lateral PFC (LPFC) compared to the neutral condition (p<0.01, whole-brain corrected). These regions were used as seed regions to further examine the connectivity patterns with other brain regions. With the VmPFC seed, AUD patients showed reduced connectivity with the anterior cingulate cortex (ACC) compared to controls, which are core regions of emotion regulation, suggesting AUD patients’ decreased ability to modulate emotional response under distressed state. With the right caudate seed, patients showed increased connectivity with the right motor cortex, suggesting increased tendency toward habitually driven behaviors. With the left LPFC seed, decreased connectivity with the dorsomedial PFC (DmPFC), but increased connectivity with sensory and motor cortices were found in AUD patients compared to controls (p<0.05, whole-brain corrected). Reduced connectivity between the left LPFC and DmPFC was further associated with increased stress-induced anxiety in AUD patients (p<0.05, with adjusted Bonferroni correction). CONCLUSION Hypoactive response to stress and altered connectivity in key emotion regulatory regions may account for greater stress-related impulse control problems in alcoholism. PMID:27501356

Neural Correlates and Connectivity Underlying Stress-Related Impulse Control Difficulties in Alcoholism.

PubMed

Seo, Dongju; Lacadie, Cheryl M; Sinha, Rajita

2016-09-01

Stress triggers impulsive and addictive behaviors, and alcoholism has been frequently associated with increased stress sensitivity and impulse control problems. However, neural correlates underlying the link between alcoholism and impulsivity in the context of stress in patients with alcohol use disorders (AUD) have not been well studied. This study investigated neural correlates and connectivity patterns associated with impulse control difficulties in abstinent AUD patients. Using functional magnetic resonance imaging, brain responses of 37 AUD inpatients, and 37 demographically matched healthy controls were examined during brief individualized imagery trials of stress, alcohol cue, and neutral-relaxing conditions. Stress-related impulsivity was measured using a subscale score of impulse control problems from Difficulties in Emotion Regulation Scale. Impulse control difficulties in AUD patients were significantly associated with hypo-active response to stress in the ventromedial prefrontal cortex (VmPFC), right caudate, and left lateral PFC (LPFC) compared to the neutral condition (p < 0.01, whole-brain corrected). These regions were used as seed regions to further examine the connectivity patterns with other brain regions. With the VmPFC seed, AUD patients showed reduced connectivity with the anterior cingulate cortex compared to controls, which are core regions of emotion regulation, suggesting AUD patients' decreased ability to modulate emotional response under distressed state. With the right caudate seed, patients showed increased connectivity with the right motor cortex, suggesting increased tendency toward habitually driven behaviors. With the left LPFC seed, decreased connectivity with the dorsomedial PFC (DmPFC), but increased connectivity with sensory and motor cortices were found in AUD patients compared to controls (p < 0.05, whole-brain corrected). Reduced connectivity between the left LPFC and DmPFC was further associated with increased stress-induced anxiety in AUD patients (p < 0.05, with adjusted Bonferroni correction). Hypo-active response to stress and altered connectivity in key emotion regulatory regions may account for greater stress-related impulse control problems in alcoholism. Copyright © 2016 by the Research Society on Alcoholism.

Amino Acids That Centrally Influence Blood Pressure and Regional Blood Flow in Conscious Rats

PubMed Central

Takemoto, Yumi

2012-01-01

Functional roles of amino acids have increasingly become the focus of research. This paper summarizes amino acids that influence cardiovascular system via the brain of conscious rats. This paper firstly describes why amino acids are selected and outlines how the brain regulates blood pressure and regional blood flow. This section includes a concise history of amino acid neurotransmitters in cardiovascular research and summarizes brain areas where chemical stimulations produce blood pressure changes mainly in anesthetized animals. This is followed by comments about findings regarding several newly examined amino acids with intracisternal stimulation in conscious rats that produce changes in blood pressure. The same pressor or depressor response to central amino acid stimulations can be produced by distinct mechanisms at central and peripheral levels, which will be briefly explained. Thereafter, cardiovascular actions of some of amino acids at the mechanism level will be discussed based upon findings of pharmacological and regional blood flow measurements. Several examined amino acids in addition to the established neurotransmitter amino acids appear to differentially activate brain structures to produce changes in blood pressure and regional blood flows. They may have physiological roles in the healthy brain, but pathological roles in the brain with cerebral vascular diseases such as stroke where the blood-brain barrier is broken. PMID:22690328

[Disturbances of cerebral perfusion in patients with bacterial meningoencephalitis].

PubMed

Garlicki, Aleksander; Podsiadło-Kleinrok, Beata; Bociaga-Jasik, Monika; Kleinrok, Krzysztof; Tomik, Barbara

2003-01-01

The investigations were done in acute and reconvalescent phase in 34 patients with bacterial meningoencephalitis. Neurologic condition, degree of the brain injury on the basis of Glasgow Coma Scale (GCS), protein level and pleocytosis in cerebrospinal fluid (CSF), and regional cerebral blood flow on dynamic computed tomography (CT) were assessed. The brain blood flow was measured in the white matter of the frontal and occipital horns of lateral ventricles, symmetrically in both hemispheres. Statistically significant reduction of the brain perfusion in acute phase of illness was improved. In reconvalescent phase normalisation of the brain blood supply was observed. 56% of patients had changes of consciousness. There was no significant correlation between these symptoms and parameters describing blood supply. The rest of patients had neurologic abnormalities: seizure, pyramidal syndrome, injury of the central nerves due to the reduction of blood flow in selected regions of the brain. Patients who aggregated low GCS score had high inflow of the blood. In patients who were in better condition, inflow was smaller. High pleocytosis in CSF was associated with small blood inflow and perfusion in investigated regions of the brain. Whereas high protein concentration correlated with higher inflow and increase in regional perfusion. We consider, that the brain blood supply correlate with intensification of inflammatory response in CSF.

The Neural Basis of Maternal Bonding

PubMed Central

Wan, Ming Wai; Downey, Darragh; Strachan, Hilary; Elliott, Rebecca; Williams, Steve R.; Abel, Kathryn M.

2014-01-01

Background Accumulating evidence suggests that mothers show a different pattern of brain responses when viewing their own compared to other infants. However, there is inconsistency across functional imaging studies regarding the key areas involved, and none have examined relationships between brain and behavioural responses to infants. We examined the brain regions activated when mothers viewed videos of their own infant contrasted with an unknown infant, and whether these are associated with behavioural and self-reported measures of mother-infant relations. Method Twenty right-handed mothers viewed alternating 30-sec blocks of video of own 4–9 month infant and an unfamiliar matched infant, interspersed with neutral video. Whole brain functional magnetic resonance images (fMRI) were acquired on a 1.5T Philips Intera scanner using a TR of 2.55 s. Videotaped mother-infant interactions were systematically evaluated blind to family information to generate behavioural measures for correlational analysis. Results Enhanced blood oxygenation functional imaging responses were found in the own versus unknown infant contrast in the bilateral precuneus, right superior temporal gyrus, right medial and left middle frontal gyri and left amygdala. Positive mother-infant interaction (less directive parent behaviour; more positive/attentive infant behaviour) was significantly associated with greater activation in several regions on viewing own versus unknown infant, particularly the middle frontal gyrus. Mothers' perceived warmth of her infant was correlated with activations in the same contrast, particularly in sensory and visual areas. Conclusion This study partially replicates previous reports of the brain regions activated in mothers in response to the visual presentation of their own infant. It is the first to report associations between mothers' unique neural responses to viewing their own infant with the quality of her concurrent behaviour when interacting with her infant and with her perceptions of infant warmth. These findings provide support for developing fMRI as a potential biomarker of parenting risk and change. PMID:24594508

The brain ages optimally to model its environment: evidence from sensory learning over the adult lifespan.

PubMed

Moran, Rosalyn J; Symmonds, Mkael; Dolan, Raymond J; Friston, Karl J

2014-01-01

The aging brain shows a progressive loss of neuropil, which is accompanied by subtle changes in neuronal plasticity, sensory learning and memory. Neurophysiologically, aging attenuates evoked responses--including the mismatch negativity (MMN). This is accompanied by a shift in cortical responsivity from sensory (posterior) regions to executive (anterior) regions, which has been interpreted as a compensatory response for cognitive decline. Theoretical neurobiology offers a simpler explanation for all of these effects--from a Bayesian perspective, as the brain is progressively optimized to model its world, its complexity will decrease. A corollary of this complexity reduction is an attenuation of Bayesian updating or sensory learning. Here we confirmed this hypothesis using magnetoencephalographic recordings of the mismatch negativity elicited in a large cohort of human subjects, in their third to ninth decade. Employing dynamic causal modeling to assay the synaptic mechanisms underlying these non-invasive recordings, we found a selective age-related attenuation of synaptic connectivity changes that underpin rapid sensory learning. In contrast, baseline synaptic connectivity strengths were consistently strong over the decades. Our findings suggest that the lifetime accrual of sensory experience optimizes functional brain architectures to enable efficient and generalizable predictions of the world.

Age-related reduction of adaptive brain response during semantic integration is associated with gray matter reduction.

PubMed

Zhu, Zude; Yang, Fengjun; Li, Dongning; Zhou, Lianjun; Liu, Ying; Zhang, Ying; Chen, Xuezhi

2017-01-01

While aging is associated with increased knowledge, it is also associated with decreased semantic integration. To investigate brain activation changes during semantic integration, a sample of forty-eight 25-75 year-old adults read sentences with high cloze (HC) and low cloze (LC) probability while functional magnetic resonance imaging was conducted. Significant age-related reduction of cloze effect (LC vs. HC) was found in several regions, especially the left middle frontal gyrus (MFG) and right inferior frontal gyrus (IFG), which play an important role in semantic integration. Moreover, when accounting for global gray matter volume reduction, the age-cloze correlation in the left MFG and right IFG was absent. The results suggest that brain structural atrophy may disrupt brain response in aging brains, which then show less brain engagement in semantic integration.

Neurobiology of culturally common maternal responses to infant cry

PubMed Central

Bornstein, Marc H.; Rigo, Paola; Esposito, Gianluca; Swain, James E.; Suwalsky, Joan T. D.; Su, Xueyun; Du, Xiaoxia; Zhang, Kaihua; Cote, Linda R.; De Pisapia, Nicola; Venuti, Paola

2017-01-01

This report coordinates assessments of five types of behavioral responses in new mothers to their own infants’ cries with neurobiological responses in new mothers to their own infants’ cries and in experienced mothers and inexperienced nonmothers to infant cries and other emotional and control sounds. We found that 684 new primipara mothers in 11 countries (Argentina, Belgium, Brazil, Cameroon, France, Kenya, Israel, Italy, Japan, South Korea, and the United States) preferentially responded to their infants’ vocalizing distress by picking up and holding and by talking to their infants, as opposed to displaying affection, distracting, or nurturing. Complementary functional magnetic resonance imaging (fMRI) analyses of brain responses to their own infants’ cries in 43 new primipara US mothers revealed enhanced activity in concordant brain territories linked to the intention to move and to speak, to process auditory stimulation, and to caregive [supplementary motor area (SMA), inferior frontal regions, superior temporal regions, midbrain, and striatum]. Further, fMRI brain responses to infant cries in 50 Chinese and Italian mothers replicated, extended, and, through parcellation, refined the results. Brains of inexperienced nonmothers activated differently. Culturally common responses to own infant cry coupled with corresponding fMRI findings to own infant and to generic infant cries identified specific, common, and automatic caregiving reactions in mothers to infant vocal expressions of distress and point to their putative neurobiological bases. Candidate behaviors embedded in the nervous systems of human caregivers lie at the intersection of evolutionary biology and developmental cultural psychology. PMID:29078366

It's in the eye of the beholder: selective attention to drink properties during tasting influences brain activation in gustatory and reward regions.

PubMed

van Rijn, Inge; de Graaf, Cees; Smeets, Paul A M

2018-04-01

Statements regarding pleasantness, taste intensity or caloric content on a food label may influence the attention consumers pay to such characteristics during consumption. There is little research on the effects of selective attention on taste perception and associated brain activation in regular drinks. The aim of this study was to investigate the effect of selective attention on hedonics, intensity and caloric content on brain responses during tasting drinks. Using functional MRI brain responses of 27 women were measured while they paid attention to the intensity, pleasantness or caloric content of fruit juice, tomato juice and water. Brain activation during tasting largely overlapped between the three selective attention conditions and was found in the rolandic operculum, insula and overlying frontal operculum, striatum, amygdala, thalamus, anterior cingulate cortex and middle orbitofrontal cortex (OFC). Brain activation was higher during selective attention to taste intensity compared to calories in the right middle OFC and during selective attention to pleasantness compared to intensity in the right putamen, right ACC and bilateral middle insula. Intensity ratings correlated with brain activation during selective attention to taste intensity in the anterior insula and lateral OFC. Our data suggest that not only the anterior insula but also the middle and lateral OFC are involved in evaluating taste intensity. Furthermore, selective attention to pleasantness engaged regions associated with food reward. Overall, our results indicate that selective attention to food properties can alter the activation of gustatory and reward regions. This may underlie effects of food labels on the consumption experience of consumers.

Neural representation of emotion regulation goals.

PubMed

Morawetz, Carmen; Bode, Stefan; Baudewig, Juergen; Jacobs, Arthur M; Heekeren, Hauke R

2016-02-01

The use of top-down cognitive control mechanisms to regulate emotional responses as circumstances change is critical for mental and physical health. Several theoretical models of emotion regulation have been postulated; it remains unclear, however, in which brain regions emotion regulation goals (e.g., the downregulation of fear) are represented. Here, we examined the neural mechanisms of regulating emotion using fMRI and identified brain regions representing reappraisal goals. Using a multimethodological analysis approach, combining standard activation-based and pattern-information analyses, we identified a distributed network of lateral frontal, temporal, and parietal regions implicated in reappraisal and within it, a core system that represents reappraisal goals in an abstract, stimulus-independent fashion. Within this core system, the neural pattern-separability in a subset of regions including the left inferior frontal gyrus, middle temporal gyrus, and inferior parietal lobe was related to the success in emotion regulation. Those brain regions might link the prefrontal control regions with the subcortical affective regions. Given the strong association of this subsystem with inner speech functions and semantic memory, we conclude that those cognitive mechanisms may be used for orchestrating emotion regulation. Hum Brain Mapp 37:600-620, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Chronic Ethanol Exposure Produces Time- and Brain Region-Dependent Changes in Gene Coexpression Networks

PubMed Central

Osterndorff-Kahanek, Elizabeth A.; Becker, Howard C.; Lopez, Marcelo F.; Farris, Sean P.; Tiwari, Gayatri R.; Nunez, Yury O.; Harris, R. Adron; Mayfield, R. Dayne

2015-01-01

Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY), nucleus accumbens (NAC), prefrontal cortex (PFC), and liver after four weekly cycles of chronic intermittent ethanol (CIE) vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000) at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600). Within each region, there was little gene overlap across time (~20%). All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global ‘rewiring‘ of coexpression systems involving glial and immune signaling as well as neuronal genes. PMID:25803291

Anxiety type modulates immediate versus delayed engagement of attention-related brain regions.

PubMed

Spielberg, Jeffrey M; De Leon, Angeline A; Bredemeier, Keith; Heller, Wendy; Engels, Anna S; Warren, Stacie L; Crocker, Laura D; Sutton, Bradley P; Miller, Gregory A

2013-09-01

Background Habituation of the fear response, critical for the treatment of anxiety, is inconsistently observed during exposure to threatening stimuli. One potential explanation for this inconsistency is differential attentional engagement with negatively valenced stimuli as a function of anxiety type. Methods The present study tested this hypothesis by examining patterns of neural habituation associated with anxious arousal, characterized by panic symptoms and immediate engagement with negatively valenced stimuli, versus anxious apprehension, characterized by engagement in worry to distract from negatively valenced stimuli. Results As predicted, the two anxiety types evidenced distinct patterns of attentional engagement. Anxious arousal was associated with immediate activation in attention-related brain regions that habituated over time, whereas anxious apprehension was associated with delayed activation in attention-related brain regions that occurred only after habituation in a worry-related brain region. Conclusions Results further elucidate mechanisms involved in attention to negatively valenced stimuli and indicate that anxiety is a heterogeneous construct with regard to attention to such stimuli.

Anxiety type modulates immediate versus delayed engagement of attention-related brain regions

PubMed Central

Spielberg, Jeffrey M; De Leon, Angeline A; Bredemeier, Keith; Heller, Wendy; Engels, Anna S; Warren, Stacie L; Crocker, Laura D; Sutton, Bradley P; Miller, Gregory A

2013-01-01

Background Habituation of the fear response, critical for the treatment of anxiety, is inconsistently observed during exposure to threatening stimuli. One potential explanation for this inconsistency is differential attentional engagement with negatively valenced stimuli as a function of anxiety type. Methods The present study tested this hypothesis by examining patterns of neural habituation associated with anxious arousal, characterized by panic symptoms and immediate engagement with negatively valenced stimuli, versus anxious apprehension, characterized by engagement in worry to distract from negatively valenced stimuli. Results As predicted, the two anxiety types evidenced distinct patterns of attentional engagement. Anxious arousal was associated with immediate activation in attention-related brain regions that habituated over time, whereas anxious apprehension was associated with delayed activation in attention-related brain regions that occurred only after habituation in a worry-related brain region. Conclusions Results further elucidate mechanisms involved in attention to negatively valenced stimuli and indicate that anxiety is a heterogeneous construct with regard to attention to such stimuli. PMID:24392275

Biases in measuring the brain: the trouble with the telencephalon.

PubMed

LaDage, Lara D; Roth, Timothy C; Pravosudov, Vladimir V

2009-01-01

When correlating behavior with particular brain regions thought responsible for the behavior, a different region of the brain is usually measured as a control region. This technique is often used to relate spatial processes with the hippocampus, while concomitantly controlling for overall brain changes by measuring the remainder of the telencephalon. We have identified two methods in the literature (the HOM and TTM) that estimate the volume of the telencephalon, although the majority of studies are ambiguous regarding the method employed in measuring the telencephalon. Of these two methods, the HOM might produce an artificial correlation between the telencephalon and the hippocampus, and this bias could result in a significant overestimation of the relative hippocampal volume and a significant underestimation of the telencephalon volume, both of which are regularly used in large comparative analyses. We suggest that future studies should avoid this method and all studies should explicitly delineate the procedures used when estimating brain volumes. Copyright 2009 S. Karger AG, Basel.

Different types of theta rhythmicity are induced by social and fearful stimuli in a network associated with social memory.

PubMed

Tendler, Alex; Wagner, Shlomo

2015-02-16

Rhythmic activity in the theta range is thought to promote neuronal communication between brain regions. In this study, we performed chronic telemetric recordings in socially behaving rats to monitor electrophysiological activity in limbic brain regions linked to social behavior. Social encounters were associated with increased rhythmicity in the high theta range (7-10 Hz) that was proportional to the stimulus degree of novelty. This modulation of theta rhythmicity, which was specific for social stimuli, appeared to reflect a brain-state of social arousal. In contrast, the same network responded to a fearful stimulus by enhancement of rhythmicity in the low theta range (3-7 Hz). Moreover, theta rhythmicity showed different pattern of coherence between the distinct brain regions in response to social and fearful stimuli. We suggest that the two types of stimuli induce distinct arousal states that elicit different patterns of theta rhythmicity, which cause the same brain areas to communicate in different modes.

Pilot test of a novel food response and attention training treatment for obesity: Brain imaging data suggest actions shape valuation.

PubMed

Stice, Eric; Yokum, Sonja; Veling, Harm; Kemps, Eva; Lawrence, Natalia S

2017-07-01

Elevated brain reward and attention region response, and weaker inhibitory region response to high-calorie food images have been found to predict future weight gain. These findings suggest that an intervention that reduces reward and attention region response and increases inhibitory control region response to such foods might reduce overeating. We conducted a randomized pilot experiment that tested the hypothesis that a multi-faceted food response and attention training with personalized high- and low-calorie food images would produce changes in behavioral and neural responses to food images and body fat compared to a control training with non-food images among community-recruited overweight/obese adults. Compared to changes observed in controls, completing the intervention was associated with significant reductions in reward and attention region response to high-calorie food images (Mean Cohen's d = 1.54), behavioral evidence of learning, reductions in palatability ratings and monetary valuation of high-calorie foods (p = 0.009, d's = 0.92), and greater body fat loss over a 4-week period (p = 0.009, d = 0.90), though body fat effects were not significant by 6-month follow-up. Results suggest that this multifaceted response and attention training intervention was associated with reduced reward and attention region responsivity to food cues, and a reduction in body fat. Because this implicit training treatment is both easy and inexpensive to deliver, and does not require top-down executive control that is necessary for negative energy balance obesity treatment, it may prove useful in treating obesity if future studies can determine how to create more enduring effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute and delayed neuroinflammatory response following experimental penetrating ballistic brain injury in the rat

PubMed Central

Williams, Anthony J; Wei, Hans H; Dave, Jitendra R; Tortella, Frank C

2007-01-01

Background Neuroinflammation following acute brain trauma is considered to play a prominent role in both the pathological and reconstructive response of the brain to injury. Here we characterize and contrast both an acute and delayed phase of inflammation following experimental penetrating ballistic brain injury (PBBI) in rats out to 7 days post-injury. Methods Quantitative real time PCR (QRT-PCR) was used to evaluate changes in inflammatory gene expression from the brain tissue of rats exposed to a unilateral frontal PBBI. Brain histopathology was assessed using hematoxylin and eosin (H&E), silver staining, and immunoreactivity for astrocytes (GFAP), microglia (OX-18) and the inflammatory proteins IL-1β and ICAM-1. Results Time course analysis of gene expression levels using QRT-PCR indicated a peak increase during the acute phase of the injury between 3–6 h for the cytokines TNF-α (8–11 fold), IL-1β (11–13 fold), and IL-6 (40–74 fold) as well as the cellular adhesion molecules VCAM (2–3 fold), ICAM-1 (7–15 fold), and E-selectin (11–13 fold). Consistent with the upregulation of pro-inflammatory genes, peripheral blood cell infiltration was a prominent post-injury event with peak levels of infiltrating neutrophils (24 h) and macrophages (72 h) observed throughout the core lesion. In regions of the forebrain immediately surrounding the lesion, strong immunoreactivity for activated astrocytes (GFAP) was observed as early as 6 h post-injury followed by prominent microglial reactivity (OX-18) at 72 h and resolution of both cell types in cortical brain regions by day 7. Delayed thalamic inflammation (remote from the primary lesion) was also observed as indicated by both microglial and astrocyte reactivity (72 h to 7 days) concomitant with the presence of fiber degeneration (silver staining). Conclusion In summary, PBBI induces both an acute and delayed neuroinflammatory response occurring in distinct brain regions, which may provide useful diagnostic information for the treatment of this type of brain injury. PMID:17605820

The neural signature of satiation is associated with ghrelin response and triglyceride metabolism

PubMed Central

Sun, Xue; Veldhuizen, Maria G; Wray, Amanda E; de Araujo, Ivan E; Sherwin, Robert S; Sinha, Rajita; Small, Dana M

2014-01-01

Eating behavior is guided by a complex interaction between signals conveying information about energy stores, food availability, and palatability. How peripheral signals regulate brain circuits that guide feeding during sensation and consumption of a palatable food is poorly understood. We used fMRI to measure brain response to a palatable food (milkshake) when n=32 participants were fasted and fed with either a fixed-portion or ad libitum meal. We found that larger post-prandial reductions in ghrelin and increases in triglycerides were associated with greater attenuation of response to the milkshake in brain regions regulating reward and feeding including the midbrain, amygdala, pallidum, hippocampus, insula and medial orbitofrontal cortex. Satiation-induced brain responses to milkshake were not related to acute changes in circulating insulin, glucose, or free fatty acids. The impact of a meal on the response to milkshake in the midbrain and dorsolateral prefrontal cortex differed depending upon whether meal termination was fixed or volitional, irrespective of the amount of food consumed. We conclude that satiation-induced changes in brain response to a palatable food are strongly and specifically associated with changes in circulating ghrelin and triglycerides and by volitional meal termination. PMID:24732416

Witnessing hateful people in pain modulates brain activity in regions associated with physical pain and reward

PubMed Central

Fox, Glenn R.; Sobhani, Mona; Aziz-Zadeh, Lisa

2013-01-01

How does witnessing a hateful person in pain compare to witnessing a likable person in pain? The current study compared the brain bases for how we perceive likable people in pain with those of viewing hateful people in pain. While social bonds are built through sharing the plight and pain of others in the name of empathy, viewing a hateful person in pain also has many potential ramifications. In this functional Magnetic Resonance Imaging (fMRI) study, Caucasian Jewish male participants viewed videos of (1) disliked, hateful, anti-Semitic individuals, and (2) liked, non-hateful, tolerant individuals in pain. The results showed that, compared with viewing liked people, viewing hateful people in pain elicited increased responses in regions associated with observation of physical pain (the insular cortex, the anterior cingulate cortex (ACC), and the somatosensory cortex), reward processing (the striatum), and frontal regions associated with emotion regulation. Functional connectivity analyses revealed connections between seed regions in the left ACC and right insular cortex with reward regions, the amygdala, and frontal regions associated with emotion regulation. These data indicate that regions of the brain active while viewing someone in pain may be more active in response to the danger or threat posed by witnessing the pain of a hateful individual more so than the desire to empathize with a likable person's pain. PMID:24167496

Differential brain responses to cries of infants with autistic disorder and typical development: an fMRI study.

PubMed

Venuti, Paola; Caria, Andrea; Esposito, Gianluca; De Pisapia, Nicola; Bornstein, Marc H; de Falco, Simona

2012-01-01

This study used fMRI to measure brain activity during adult processing of cries of infants with autistic disorder (AD) compared to cries of typically developing (TD) infants. Using whole brain analysis, we found that cries of infants with AD compared to those of TD infants elicited enhanced activity in brain regions associated with verbal and prosodic processing, perhaps because altered acoustic patterns of AD cries render them especially difficult to interpret, and increased activity in brain regions associated with emotional processing, indicating that AD cries also elicit more negative feelings and may be perceived as more aversive and/or arousing. Perceived distress engendered by AD cries related to increased activation in brain regions associated with emotional processing. This study supports the hypothesis that cry is an early and meaningful anomaly displayed by children with AD. It could be that cries associated with AD alter parent-child interactions much earlier than the time that reliable AD diagnosis normally occurs. Copyright © 2012 Elsevier Ltd. All rights reserved.

A SPECT study of language and brain reorganization three years after pediatric brain injury.

PubMed

Chiu Wong, Stephanie B; Chapman, Sandra B; Cook, Lois G; Anand, Raksha; Gamino, Jacquelyn F; Devous, Michael D

2006-01-01

Using single photon emission computed tomography (SPECT), we investigated brain plasticity in children 3 years after sustaining a severe traumatic brain injury (TBI). First, we assessed brain perfusion patterns (i.e., the extent of brain blood flow to regions of the brain) at rest in eight children who suffered severe TBI as compared to perfusion patterns in eight normally developing children. Second, we examined differences in perfusion between children with severe TBI who showed good versus poor recovery in complex discourse skills. Specifically, the children were asked to produce and abstract core meaning for two stories in the form of a lesson. Inconsistent with our predictions, children with severe TBI showed areas of increased perfusion as compared to normally developing controls. Adult studies have shown the reverse pattern with TBI associated with reduced perfusion. With regard to the second aim and consistent with previously identified brain-discourse relations, we found a strong positive association between perfusion in right frontal regions and discourse abstraction abilities, with higher perfusion linked to better discourse outcomes and lower perfusion linked to poorer discourse outcomes. Furthermore, brain-discourse patterns of increased perfusion in left frontal regions were associated with lower discourse abstraction ability. The results are discussed in terms of how brain changes may represent adaptive and maladaptive plasticity. The findings offer direction for future studies of brain plasticity in response to neurocognitive treatments.

Activation of writing-specific brain regions when reading Chinese as a second language. Effects of training modality and transfer to novel characters.

PubMed

Lagarrigue, Aurélie; Longcamp, Marieke; Anton, Jean Luc; Nazarian, Bruno; Prévot, Laurent; Velay, Jean-Luc; Cao, Fan; Frenck-Mestre, Cheryl

2017-03-01

We examined the implication of training modality on the cortical representation of Chinese words in adult second language learners of Chinese. In particular, we tested the implication of the neural substrates of writing in a reading task. The brain network sustaining finger writing was defined neuroanatomically based on an independent functional localizer. We examined the brain activations elicited by Chinese words learned via writing vs. pronunciation, and by novel untrained words, within regions of interest (ROIs) defined according to the position of the activation peaks in the localizer, and at the whole brain level. We revealed activations in the reading task that overlapped with several parts of the finger writing network. In addition, our results provide evidence that the neural substrates of writing are differentially involved in reading depending on the stored knowledge for words, as revealed by the fine-grained response of several regions including the left superior parietal lobule and left precentral gyrus / superior frontal sulcus to the experimental manipulations. Training modality and the linguistic properties of the characters also impacted the response of the left mid-fusiform gyrus, confirming its involvement as the brain region where linguistic, visual and sensorimotor information converge during orthographic processing. At the behavioral level, global handwriting quality during the training sessions was positively correlated to the final translation performance. Our results demonstrate substantial overlap in the neural substrates of reading and writing, and indicate that some regions sustaining handwriting are differentially involved in reading depending on the type of knowledge associated with words. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differential DNA damage in response to the neonatal and adult excitotoxic hippocampal lesion in rats.

PubMed

Khaing, Z Z; Weickert, C S; Weinberger, D R; Lipska, B K

2000-12-01

We examined the developmental profile of excitotoxin-induced nuclear DNA fragmentation using the transferase dUTP nick-end labelling (TUNEL) technique, as a marker of DNA damage and cell death in rats with neonatal and adult excitotoxic lesions of the ventral hippocampus. We hypothesized that infusion of neurotoxin may result in a differential pattern of cell death in neonatally and adult lesioned rats, both in the infusion site and in remote brain regions presumably involved in mediating behavioural changes observed in these animals. Brains of rats lesioned at 7 days of age and in adulthood were collected at several survival times 1-21 days after the lesion. In the lesioned neonates 1-3 days postlesion, marked increases in TUNEL-positive cells occurred in the ventral hippocampus, the site of neurotoxin infusion, and in a wide surrounding area. Adult lesioned brains showed more positive cells than controls only at the infusion site. In the lesioned neonates, TUNEL-labelled cells were also present in the striatum and nucleus accumbens 1 day postlesion but not at later survival times. Our findings indicate that cell death in remote regions is more prominent in immature than adult brains, that it may lead to distinct alterations in development of these brain regions, and thus may be responsible for functional differences between neonatally and adult lesioned rats.

Neural and Behavioral Responses During Self-Evaluative Processes Differ in Youth With and Without Autism

PubMed Central

Merchant, Junaid S.; Colich, Natalie L.; Hernandez, Leanna M.; Rudie, Jeff D.; Dapretto, Mirella

2012-01-01

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 middle cingulate cortex (MCC) and anterior insula (AI) also distinguished between groups. Stronger activity in MCC and AI during self-appraisals was associated with better social functioning in the ASD group. Although self-appraisals were significantly more positive in the neurotypical group, positivity was unrelated to brain activity in these regions. Together, these results suggest that multiple brain regions support making self-appraisals in neurotypical development, and function atypically in youth with ASD. PMID:22760337

Oxidative Damage in the Guinea Pig Hippocampal Slice

DTIC Science & Technology

1989-01-01

Original Contribution OXIDATIVE DAMAGE IN THE GUINEA PIG HIPPOCAMPAL SLICE TIRRY C. Pnt.N1.iAR’ and KATIlRNN L. Nt-t-t- Physiology Department. Armed Forces...responses in the hippocampal slice isolated from the brains of guinea pigs . Electrical stim- ulation of afferents to neurons of the CA I region of...from the brains be secreted by the microglia invading a region of in- of euthanized male Hartley guinea pigs as previously Jury. ’ Another possible

Consumption of fermented milk product with probiotic modulates brain activity.

PubMed

Tillisch, Kirsten; Labus, Jennifer; Kilpatrick, Lisa; Jiang, Zhiguo; Stains, Jean; Ebrat, Bahar; Guyonnet, Denis; Legrain-Raspaud, Sophie; Trotin, Beatrice; Naliboff, Bruce; Mayer, Emeran A

2013-06-01

Changes in gut microbiota have been reported to alter signaling mechanisms, emotional behavior, and visceral nociceptive reflexes in rodents. However, alteration of the intestinal microbiota with antibiotics or probiotics has not been shown to produce these changes in humans. We investigated whether consumption of a fermented milk product with probiotic (FMPP) for 4 weeks by healthy women altered brain intrinsic connectivity or responses to emotional attention tasks. Healthy women with no gastrointestinal or psychiatric symptoms were randomly assigned to groups given FMPP (n = 12), a nonfermented milk product (n = 11, controls), or no intervention (n = 13) twice daily for 4 weeks. The FMPP contained Bifidobacterium animalis subsp Lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, and Lactococcus lactis subsp Lactis. Participants underwent functional magnetic resonance imaging before and after the intervention to measure brain response to an emotional faces attention task and resting brain activity. Multivariate and region of interest analyses were performed. FMPP intake was associated with reduced task-related response of a distributed functional network (49% cross-block covariance; P = .004) containing affective, viscerosensory, and somatosensory cortices. Alterations in intrinsic activity of resting brain indicated that ingestion of FMPP was associated with changes in midbrain connectivity, which could explain the observed differences in activity during the task. Four-week intake of an FMPP by healthy women affected activity of brain regions that control central processing of emotion and sensation. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Spatiotemporal reconstruction of auditory steady-state responses to acoustic amplitude modulations: Potential sources beyond the auditory pathway.

PubMed

Farahani, Ehsan Darestani; Goossens, Tine; Wouters, Jan; van Wieringen, Astrid

2017-03-01

Investigating the neural generators of auditory steady-state responses (ASSRs), i.e., auditory evoked brain responses, with a wide range of screening and diagnostic applications, has been the focus of various studies for many years. Most of these studies employed a priori assumptions regarding the number and location of neural generators. The aim of this study is to reconstruct ASSR sources with minimal assumptions in order to gain in-depth insight into the number and location of brain regions that are activated in response to low- as well as high-frequency acoustically amplitude modulated signals. In order to reconstruct ASSR sources, we applied independent component analysis with subsequent equivalent dipole modeling to single-subject EEG data (young adults, 20-30 years of age). These data were based on white noise stimuli, amplitude modulated at 4, 20, 40, or 80Hz. The independent components that exhibited a significant ASSR were clustered among all participants by means of a probabilistic clustering method based on a Gaussian mixture model. Results suggest that a widely distributed network of sources, located in cortical as well as subcortical regions, is active in response to 4, 20, 40, and 80Hz amplitude modulated noises. Some of these sources are located beyond the central auditory pathway. Comparison of brain sources in response to different modulation frequencies suggested that the identified brain sources in the brainstem, the left and the right auditory cortex show a higher responsiveness to 40Hz than to the other modulation frequencies. Copyright © 2017 Elsevier Inc. All rights reserved.

Peer Influence Via Instagram: Effects on Brain and Behavior in Adolescence and Young Adulthood.

PubMed

Sherman, Lauren E; Greenfield, Patricia M; Hernandez, Leanna M; Dapretto, Mirella

2018-01-01

Mobile social media often feature the ability to "Like" content posted by others. This study examined the effect of Likes on youths' neural and behavioral responses to photographs. High school and college students (N = 61, ages 13-21) viewed theirs and others' Instagram photographs while undergoing functional Magnetic Resonance Imaging (fMRI). Participants more often Liked photographs that appeared to have received many (vs. few) Likes. Popular photographs elicited greater activity in multiple brain regions, including the nucleus accumbens (NAcc), a hub of the brain's reward circuitry. NAcc responsivity increased with age for high school but not college students. When viewing images depicting risk-taking (vs. nonrisky photographs), high school students, but not college students, showed decreased activation of neural regions implicated in cognitive control. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

Mapping human temporal and parietal neuronal population activity and functional coupling during mathematical cognition

PubMed Central

Daitch, Amy L.; Foster, Brett L.; Schrouff, Jessica; Rangarajan, Vinitha; Kaşikçi, Itır; Gattas, Sandra; Parvizi, Josef

2016-01-01

Brain areas within the lateral parietal cortex (LPC) and ventral temporal cortex (VTC) have been shown to code for abstract quantity representations and for symbolic numerical representations, respectively. To explore the fast dynamics of activity within each region and the interaction between them, we used electrocorticography recordings from 16 neurosurgical subjects implanted with grids of electrodes over these two regions and tracked the activity within and between the regions as subjects performed three different numerical tasks. Although our results reconfirm the presence of math-selective hubs within the VTC and LPC, we report here a remarkable heterogeneity of neural responses within each region at both millimeter and millisecond scales. Moreover, we show that the heterogeneity of response profiles within each hub mirrors the distinct patterns of functional coupling between them. Our results support the existence of multiple bidirectional functional loops operating between discrete populations of neurons within the VTC and LPC during the visual processing of numerals and the performance of arithmetic functions. These findings reveal information about the dynamics of numerical processing in the brain and also provide insight into the fine-grained functional architecture and connectivity within the human brain. PMID:27821758

Random Forest Segregation of Drug Responses May Define Regions of Biological Significance.

PubMed

Bukhari, Qasim; Borsook, David; Rudin, Markus; Becerra, Lino

2016-01-01

The ability to assess brain responses in unsupervised manner based on fMRI measure has remained a challenge. Here we have applied the Random Forest (RF) method to detect differences in the pharmacological MRI (phMRI) response in rats to treatment with an analgesic drug (buprenorphine) as compared to control (saline). Three groups of animals were studied: two groups treated with different doses of the opioid buprenorphine, low (LD), and high dose (HD), and one receiving saline. PhMRI responses were evaluated in 45 brain regions and RF analysis was applied to allocate rats to the individual treatment groups. RF analysis was able to identify drug effects based on differential phMRI responses in the hippocampus, amygdala, nucleus accumbens, superior colliculus, and the lateral and posterior thalamus for drug vs. saline. These structures have high levels of mu opioid receptors. In addition these regions are involved in aversive signaling, which is inhibited by mu opioids. The results demonstrate that buprenorphine mediated phMRI responses comprise characteristic features that allow a supervised differentiation from placebo treated rats as well as the proper allocation to the respective drug dose group using the RF method, a method that has been successfully applied in clinical studies.

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

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.

Fuel not fun: Reinterpreting attenuated brain responses to reward in obesity.

PubMed

Kroemer, Nils B; Small, Dana M

2016-08-01

There is a well-established literature linking obesity to altered dopamine signaling and brain response to food-related stimuli. Neuroimaging studies frequently report enhanced responses in dopaminergic regions during food anticipation and decreased responses during reward receipt. This has been interpreted as reflecting anticipatory "reward surfeit", and consummatory "reward deficiency". In particular, attenuated response in the dorsal striatum to primary food rewards is proposed to reflect anhedonia, which leads to overeating in an attempt to compensate for the reward deficit. In this paper, we propose an alternative view. We consider brain response to food-related stimuli in a reinforcement-learning framework, which can be employed to separate the contributions of reward sensitivity and reward-related learning that are typically entangled in the brain response to reward. Consequently, we posit that decreased striatal responses to milkshake receipt reflect reduced reward-related learning rather than reward deficiency or anhedonia because reduced reward sensitivity would translate uniformly into reduced anticipatory and consummatory responses to reward. By re-conceptualizing reward deficiency as a shift in learning about subjective value of rewards, we attempt to reconcile neuroimaging findings with the putative role of dopamine in effort, energy expenditure and exploration and suggest that attenuated brain responses to energy dense foods reflect the "fuel", not the fun entailed by the reward. Copyright © 2016 Elsevier Inc. All rights reserved.

Episodic Memory in Detoxified Alcoholics: Contribution of Grey Matter Microstructure Alteration

PubMed Central

Chanraud, Sandra; Leroy, Claire; Martelli, Catherine; Kostogianni, Nikoleta; Delain, Françoise; Aubin, Henri-Jean; Reynaud, Michel; Martinot, Jean-Luc

2009-01-01

Even though uncomplicated alcoholics may likely have episodic memory deficits, discrepancies exist regarding to the integrity of brain regions that underlie this function in healthy subjects. Possible relationships between episodic memory and 1) brain microstructure assessed by magnetic resonance diffusion tensor imaging (DTI), 2) brain volumes assessed by voxel-based morphometry (VBM) were investigated in uncomplicated, detoxified alcoholics. Diffusion and morphometric analyses were performed in 24 alcohol dependent men without neurological or somatic complications and in 24 healthy men. The mean apparent coefficient of diffusion (ADC) and grey matter volumes were measured in the whole brain. Episodic memory performance was assessed using a French version of the Free and Cued Selective Reminding Test (FCSRT). Correlation analyses between verbal episodic memory, brain microstructure, and brain volumes were carried out using SPM2 software. In those with alcohol dependence, higher ADC was detected mainly in frontal, temporal and parahippocampal regions, and in the cerebellum. In alcoholics, regions with higher ADC typically also had lower grey matter volume. Low verbal episodic memory performance in alcoholism was associated with higher mean ADC in parahippocampal areas, in frontal cortex and in the left temporal cortex; no correlation was found between regional volumes and episodic memory scores. Regression analyses for the control group were not significant. These findings support the hypothesis that regional microstructural but no macrostructural alteration of the brain might be responsible, at least in part, for episodic memory deficits in alcohol dependence. PMID:19707568

Fear across the senses: brain responses to music, vocalizations and facial expressions

PubMed Central

Angulo-Perkins, Arafat; Peretz, Isabelle; Concha, Luis; Armony, Jorge L.

2015-01-01

Intrinsic emotional expressions such as those communicated by faces and vocalizations have been shown to engage specific brain regions, such as the amygdala. Although music constitutes another powerful means to express emotions, the neural substrates involved in its processing remain poorly understood. In particular, it is unknown whether brain regions typically associated with processing ‘biologically relevant’ emotional expressions are also recruited by emotional music. To address this question, we conducted an event-related functional magnetic resonance imaging study in 47 healthy volunteers in which we directly compared responses to basic emotions (fear, sadness and happiness, as well as neutral) expressed through faces, non-linguistic vocalizations and short novel musical excerpts. Our results confirmed the importance of fear in emotional communication, as revealed by significant blood oxygen level-dependent signal increased in a cluster within the posterior amygdala and anterior hippocampus, as well as in the posterior insula across all three domains. Moreover, subject-specific amygdala responses to fearful music and vocalizations were correlated, consistent with the proposal that the brain circuitry involved in the processing of musical emotions might be shared with the one that have evolved for vocalizations. Overall, our results show that processing of fear expressed through music, engages some of the same brain areas known to be crucial for detecting and evaluating threat-related information. PMID:24795437

Fear across the senses: brain responses to music, vocalizations and facial expressions.

PubMed

Aubé, William; Angulo-Perkins, Arafat; Peretz, Isabelle; Concha, Luis; Armony, Jorge L

2015-03-01

Intrinsic emotional expressions such as those communicated by faces and vocalizations have been shown to engage specific brain regions, such as the amygdala. Although music constitutes another powerful means to express emotions, the neural substrates involved in its processing remain poorly understood. In particular, it is unknown whether brain regions typically associated with processing 'biologically relevant' emotional expressions are also recruited by emotional music. To address this question, we conducted an event-related functional magnetic resonance imaging study in 47 healthy volunteers in which we directly compared responses to basic emotions (fear, sadness and happiness, as well as neutral) expressed through faces, non-linguistic vocalizations and short novel musical excerpts. Our results confirmed the importance of fear in emotional communication, as revealed by significant blood oxygen level-dependent signal increased in a cluster within the posterior amygdala and anterior hippocampus, as well as in the posterior insula across all three domains. Moreover, subject-specific amygdala responses to fearful music and vocalizations were correlated, consistent with the proposal that the brain circuitry involved in the processing of musical emotions might be shared with the one that have evolved for vocalizations. Overall, our results show that processing of fear expressed through music, engages some of the same brain areas known to be crucial for detecting and evaluating threat-related information. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Markers of oxidative damage to lipids, nucleic acids and proteins and antioxidant enzymes activities in Alzheimer's disease brain: A meta-analysis in human pathological specimens.

PubMed

Zabel, Matthew; Nackenoff, Alex; Kirsch, Wolff M; Harrison, Fiona E; Perry, George; Schrag, Matthew

2018-02-01

Oxidative stress and decreased cellular responsiveness to oxidative stress are thought to influence brain aging and Alzheimer's disease, but the specific patterns of oxidative damage and the underlying mechanism leading to this damage are not definitively known. The objective of this study was to define the pattern of changes in oxidative-stress related markers by brain region in human Alzheimer's disease and mild cognitive impairment brain tissue. Observational case-control studies were identified from systematic queries of PubMed, ISI Web of Science and Scopus databases and studies were evaluated with appropriate quality measures. The data was used to construct a region-by-region meta-analysis of malondialdehyde, 4-hydroxynonenal, protein carbonylation, 8-hydroxyguanine levels and superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase activities. We also evaluated ascorbic acid, tocopherol, uric acid and glutathione levels. The analysis was complicated in several cases by publication bias and/or outlier data. We found that malondialdehyde levels were slightly increased in the temporal and occipital lobes and hippocampus, but this analysis was significantly impacted by publication bias. 4-hydroxynonenal levels were unchanged in every brain region. There was no change in 8-hydroxyguanine level in any brain region and protein carbonylation levels were unchanged except for a slight increase in the occipital lobe. Superoxide dismutase, glutathione peroxidase and reductase and catalase activities were not decreased in any brain region. There was limited data reporting non-enzymatic antioxidant levels in Alzheimer's disease brain, although glutathione and tocopherol levels appear to be unchanged. Minimal quantitative data is available from brain tissue from patients with mild cognitive impairment. While there is modest evidence supporting minor regional changes in markers of oxidative damage, this analysis fails to identify a consistent pattern of pro-oxidative changes and accumulation of oxidative damage in bulk tissue analysis in the setting of Alzheimer's disease, as has been widely reported. Copyright © 2017 Elsevier Inc. All rights reserved.

Fear and Reward Circuit Alterations in Pediatric CRPS.

PubMed

Simons, Laura E; Erpelding, Nathalie; Hernandez, Jessica M; Serrano, Paul; Zhang, Kunyu; Lebel, Alyssa A; Sethna, Navil F; Berde, Charles B; Prabhu, Sanjay P; Becerra, Lino; Borsook, David

2015-01-01

In chronic pain, a number of brain regions involved in emotion (e.g., amygdala, hippocampus, nucleus accumbens, insula, anterior cingulate, and prefrontal cortex) show significant functional and morphometric changes. One phenotypic manifestation of these changes is pain-related fear (PRF). PRF is associated with profoundly altered behavioral adaptations to chronic pain. For example, patients with a neuropathic pain condition known as complex regional pain syndrome (CRPS) often avoid use of and may even neglect the affected body area(s), thus maintaining and likely enhancing PRF. These changes form part of an overall maladaptation to chronic pain. To examine fear-related brain circuit alterations in humans, 20 pediatric patients with CRPS and 20 sex- and age-matched healthy controls underwent functional magnetic resonance imaging (fMRI) in response to a well-established fearful faces paradigm. Despite no significant differences on self-reported emotional valence and arousal between the two groups, CRPS patients displayed a diminished response to fearful faces in regions associated with emotional processing compared to healthy controls. Additionally, increased PRF levels were associated with decreased activity in a number of brain regions including the right amygdala, insula, putamen, and caudate. Blunted activation in patients suggests that (a) individuals with chronic pain may have deficits in cognitive-affective brain circuits that may represent an underlying vulnerability or consequence to the chronic pain state; and (b) fear of pain may contribute and/or maintain these brain alterations. Our results shed new light on altered affective circuits in patients with chronic pain and identify PRF as a potentially important treatment target.

Brain regions implicated in inhibitory control and appetite regulation are activated in response to food portion size and energy density in children.

PubMed

English, L K; Fearnbach, S N; Lasschuijt, M; Schlegel, A; Anderson, K; Harris, S; Wilson, S J; Fisher, J O; Savage, J S; Rolls, B J; Keller, K L

2016-10-01

Large portions of energy-dense foods drive energy intake but the brain mechanisms underlying this effect are not clear. Our main objective was to investigate brain function in response to food images varied by portion size (PS) and energy density (ED) in children using functional magnetic resonance imaging (fMRI). Blood-oxygen-level-dependent (BOLD) fMRI was completed in 36 children (ages 7-10 years) after a 2-h fast while viewing food images at two levels of PS (Large PS, Small PS) and two levels of ED (High ED, Low ED). Children rated perceived fullness pre- and post-fMRI, as well as liking of images on visual analog scales post-fMRI. Anthropometrics were completed 4 weeks before the fMRI. Large PS vs Small PS and High ED vs Low ED were compared with region-of-interest analyses using Brain Voyager v 2.8. Region-of-interest analyses revealed that activation in the right inferior frontal gyrus (P=0.03) was greater for Large PS vs Small PS. Activation was reduced for High ED vs Low ED in the left hypothalamus (P=0.03). Main effects were no longer significant after adjustment for pre-fMRI fullness and liking ratings (PS, P=0.92; ED, P=0.58). This is the first fMRI study to report increased activation to large portions in a brain region that is involved in inhibitory control. These findings may contribute to understanding why some children overeat when presented with large portions of palatable food.

Lateralization of brain activation to imagination and smell of odors using functional magnetic resonance imaging (fMRI): left hemispheric localization of pleasant and right hemispheric localization of unpleasant odors.

PubMed

Henkin, R I; Levy, L M

2001-01-01

Our goal was to use functional MRI (fMRI) of brain to reveal activation in each cerebral hemisphere in response to imagination and smell of odors. FMRI brain scans were obtained in 24 normal subjects using multislice fast low angle shot (FLASH) MRI in response to imagination of banana and peppermint odors and in response to smell of corresponding odors of amyl acetate and menthone, respectively, and of pyridine. Three coronal sections selected from anterior to posterior brain regions were used. Similar studies were obtained in two patients with hyposmia using FLASH MRI and in one patient with hyposmia using echo planar imaging (EPI) both before and after theophylline treatment that returned smell function to or toward normal in each patient and in two patients with birhinal phantosmia (persistent foul odor) and global phantogeusia (persistent foul taste) with FLASH and EPI fMRI before and after treatment with neuroleptic drugs that inhibited their phantosmia and phantogeusia. Activation images were derived using correlation analysis. Ratios of hemispheric areas of brain activation to total hemispheric brain areas were calculated for FLASH fMRI, and numerical counts of pixel clusters in each hemisphere were made for EPI studies. Total pixel cluster counts in localized regions of each hemispheric section were also obtained. In normal subjects, activation generally occurred in left (L) > right (R) brain hemisphere in response to banana and peppermint odor imagination and to smell of corresponding odors of amyl acetate and menthone. Whereas there were no overall hemispheric differences for pyridine odor, activation in men was R > L hemisphere. Although absolute activation in both L and R hemispheres in response to banana odor imagination and amyl acetate smell was men > women, the ratio of L to R activation was women > men. In hyposmic patients studied by FLASH fMRI, activation to banana odor imagination and amyl acetate smell was L > R hemisphere both before and after theophylline treatment. In the hyposmic patient studied with EPI before theophylline treatment, activation to banana and peppermint odor imagination and to amyl acetate, menthone, and pyridine smell was R > L hemisphere; after theophylline treatment restored normal smell function, activation shifted completely with banana and peppermint odor imagination and amyl acetate and menthone smell to L > R hemisphere, consistent with responses in normal subjects. However, this shift also occurred for pyridine smell, which is opposite to responses in normal control subjects. In patients with phantosmia and phantogeusia, activation to phantosmia and phantogeusia before treatment was R > L hemisphere; after treatment inhibited phantosmia and phantogeusia, activation shifted with a slight L > R hemispheric lateralization. Localization of all lateralized responses indicated that anterior frontal and temporal cortices were brain regions most involved with imagination and smell of odors and with phantosmia and phantogeusia presence. Imagination and smell of odors perceived as pleasant generally activated the dominant or L > R brain hemisphere. Smell of odors perceived as unpleasant and unpleasant phantosmia and phantogeusia generally activated the contralateral or R > L brain hemisphere. With remission of phantosmia and phantogeusia, hemispheric activation was not only inhibited, but also there was a slight shift to L > R hemispheric predominance. Predominant L > R hemispheric differences in brain activation in normal subjects occurred in the order amyl acetate > menthone > pyridine, consistent with the hypothesis that pleasant odors are more appreciated in L hemisphere and unpleasant odors more in R hemisphere. Anterior frontal and temporal cortex regions previously found activated by imagination and smell of odors and phantosmia and phantogeusia perception accounted for most hemispheric differences.

Task alters category representations in prefrontal but not high-level visual cortex.

PubMed

Bugatus, Lior; Weiner, Kevin S; Grill-Spector, Kalanit

2017-07-15

A central question in neuroscience is how cognitive tasks affect category representations across the human brain. Regions in lateral occipito-temporal cortex (LOTC), ventral temporal cortex (VTC), and ventro-lateral prefrontal cortex (VLFPC) constitute the extended "what" pathway, which is considered instrumental for visual category processing. However, it is unknown (1) whether distributed responses across LOTC, VTC, and VLPFC explicitly represent category, task, or some combination of both, and (2) in what way representations across these subdivisions of the extended 'what' pathway may differ. To fill these gaps in knowledge, we scanned 12 participants using fMRI to test the effect of category and task on distributed responses across LOTC, VTC, and VLPFC. Results reveal that task and category modulate responses in both high-level visual regions, as well as prefrontal cortex. However, we found fundamentally different types of representations across the brain. Distributed responses in high-level visual regions are more strongly driven by category than task, and exhibit task-independent category representations. In contrast, distributed responses in prefrontal cortex are more strongly driven by task than category, and contain task-dependent category representations. Together, these findings of differential representations across the brain support a new idea that LOTC and VTC maintain stable category representations allowing efficient processing of visual information, while prefrontal cortex contains flexible representations in which category information may emerge only when relevant to the task. Copyright © 2017 Elsevier Inc. All rights reserved.

Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

PubMed Central

Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

2015-01-01

Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

Experiential, autonomic, and neural responses during threat anticipation vary as a function of threat intensity and neuroticism.

PubMed

Drabant, Emily M; Kuo, Janice R; Ramel, Wiveka; Blechert, Jens; Edge, Michael D; Cooper, Jeff R; Goldin, Philippe R; Hariri, Ahmad R; Gross, James J

2011-03-01

Anticipatory emotional responses play a crucial role in preparing individuals for impending challenges. They do this by triggering a coordinated set of changes in behavioral, autonomic, and neural response systems. In the present study, we examined the biobehavioral impact of varying levels of anticipatory anxiety, using a shock anticipation task in which unpredictable electric shocks were threatened and delivered to the wrist at variable intervals and intensities (safe, medium, strong). This permitted investigation of a dynamic range of anticipatory anxiety responses. In two studies, 95 and 51 healthy female participants, respectively, underwent this shock anticipation task while providing continuous ratings of anxiety experience and electrodermal responding (Study 1) and during fMRI BOLD neuroimaging (Study 2). Results indicated a step-wise pattern of responding in anxiety experience and electrodermal responses. Several brain regions showed robust responses to shock anticipation relative to safe trials, including the hypothalamus, periaqueductal gray, caudate, precentral gyrus, thalamus, insula, ventrolateral PFC, dorsomedial PFC, and ACC. A subset of these regions demonstrated a linear pattern of increased responding from safe to medium to strong trials, including the bilateral insula, ACC, and inferior frontal gyrus. These responses were modulated by individual differences in neuroticism, such that those high in neuroticism showed exaggerated anxiety experience across the entire task, and reduced brain activation from medium to strong trials in a subset of brain regions. These findings suggest that individual differences in neuroticism may influence sensitivity to anticipatory threat and provide new insights into the mechanism through which neuroticism may confer risk for developing anxiety disorders via dysregulated anticipatory responses. Copyright © 2010 Elsevier Inc. All rights reserved.

The Richness of Task-Evoked Hemodynamic Responses Defines a Pseudohierarchy of Functionally Meaningful Brain Networks

PubMed Central

Orban, Pierre; Doyon, Julien; Petrides, Michael; Mennes, Maarten; Hoge, Richard; Bellec, Pierre

2015-01-01

Functional magnetic resonance imaging can measure distributed and subtle variations in brain responses associated with task performance. However, it is unclear whether the rich variety of responses observed across the brain is functionally meaningful and consistent across individuals. Here, we used a multivariate clustering approach that grouped brain regions into clusters based on the similarity of their task-evoked temporal responses at the individual level, and then established the spatial consistency of these individual clusters at the group level. We observed a stable pseudohierarchy of task-evoked networks in the context of a delayed sequential motor task, where the fractionation of networks was driven by a gradient of involvement in motor sequence preparation versus execution. In line with theories about higher-level cognitive functioning, this gradient evolved in a rostro-caudal manner in the frontal lobe. In addition, parcellations in the cerebellum and basal ganglia matched with known anatomical territories and fiber pathways with the cerebral cortex. These findings demonstrate that subtle variations in brain responses associated with task performance are systematic enough across subjects to define a pseudohierarchy of task-evoked networks. Such networks capture meaningful functional features of brain organization as shaped by a given cognitive context. PMID:24729172

Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain.

PubMed

Sawicki, C M; McKim, D B; Wohleb, E S; Jarrett, B L; Reader, B F; Norden, D M; Godbout, J P; Sheridan, J F

2015-08-27

Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b(+) cells (microglia/macrophages) and enriched GLAST-1(+)/CD11b(-) cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain region-dependent manner. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain

PubMed Central

Sawicki, Caroline M.; McKim, Daniel B.; Wohleb, Eric S.; Jarrett, Brant L.; Reader, Brenda F.; Norden, Diana M.; Godbout, Jonathan P.; Sheridan, John F.

2014-01-01

Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain-myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b+ cells (microglia/macrophages) and enriched GLAST-1+/CD11b− cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain-region dependent manner. PMID:25445193

Individual Functional ROI Optimization via Maximization of Group-wise Consistency of Structural and Functional Profiles

PubMed Central

Li, Kaiming; Guo, Lei; Zhu, Dajiang; Hu, Xintao; Han, Junwei; Liu, Tianming

2013-01-01

Studying connectivities among functional brain regions and the functional dynamics on brain networks has drawn increasing interest. A fundamental issue that affects functional connectivity and dynamics studies is how to determine the best possible functional brain regions or ROIs (regions of interest) for a group of individuals, since the connectivity measurements are heavily dependent on ROI locations. Essentially, identification of accurate, reliable and consistent corresponding ROIs is challenging due to the unclear boundaries between brain regions, variability across individuals, and nonlinearity of the ROIs. In response to these challenges, this paper presents a novel methodology to computationally optimize ROIs locations derived from task-based fMRI data for individuals so that the optimized ROIs are more consistent, reproducible and predictable across brains. Our computational strategy is to formulate the individual ROI location optimization as a group variance minimization problem, in which group-wise consistencies in functional/structural connectivity patterns and anatomic profiles are defined as optimization constraints. Our experimental results from multimodal fMRI and DTI data show that the optimized ROIs have significantly improved consistency in structural and functional profiles across individuals. These improved functional ROIs with better consistency could contribute to further study of functional interaction and dynamics in the human brain. PMID:22281931

Brain Region–Specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components during Peripheral Endotoxin–Induced Inflammation

PubMed Central

Silverman, Harold A; Dancho, Meghan; Regnier-Golanov, Angelique; Nasim, Mansoor; Ochani, Mahendar; Olofsson, Peder S; Ahmed, Mohamed; Miller, Edmund J; Chavan, Sangeeta S; Golanov, Eugene; Metz, Christine N; Tracey, Kevin J; Pavlov, Valentin A

2014-01-01

Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune–brain communication, including the impact of peripheral inflammation on brain region–specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region–specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat ) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches. PMID:25299421

Frequency analysis of the visual steady-state response measured with the fast optical signal in younger and older adults.

PubMed

Tse, Chun-Yu; Gordon, Brian A; Fabiani, Monica; Gratton, Gabriele

2010-09-01

Relatively high frequency activity (>4Hz) carries important information about the state of the brain or its response to high frequency events. The electroencephalogram (EEG) is commonly used to study these changes because it possesses high temporal resolution and a good signal-to-noise ratio. However, it provides limited spatial information. Non-invasive fast optical signals (FOS) have been proposed as a neuroimaging tool combining spatial and temporal resolution. Yet, this technique has not been applied to study high frequency brain oscillations because of its relatively low signal-to-noise ratio. Here we investigate the sensitivity of FOS to relatively high-frequency brain oscillations. We measured the steady-state optical response elicited in medial and lateral occipital cortex by checkerboard reversals occurring at 4, 6, and 8Hz in younger and older adults. Stimulus-dependent oscillations were observed at the predicted stimulation frequency. In addition, in the younger adults the FOS steady-state response was smaller in lateral than medial areas, whereas in the older adults it was reversed in these two cortical regions. This may reflect diminished top-down inhibitory control in the older adults. The results indicate that FOS can be used to study the modulation of relatively high-frequency brain oscillations in adjacent cortical regions. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Influence of Alcohol Use on Neural Response to Go/No-Go Task in College Drinkers

PubMed Central

Ahmadi, Aral; Pearlson, Godfrey D; Meda, Shashwath A; Dager, Alecia; Potenza, Marc N; Rosen, Rivkah; Austad, Carol S; Raskin, Sarah A; Fallahi, Carolyn R; Tennen, Howard; Wood, Rebecca M; Stevens, Michael C

2013-01-01

Impaired inhibition of prepotent motor response may represent an important risk factor for alcoholism. Alcohol use may also increase impulsive behavior, including impaired response inhibition. Little is known about the brain function underlying response inhibition among college-age drinkers based on their drinking patterns, despite college-age drinkers demonstrating high rates of alcohol-use disorders. Our major objective was to compare behavior and associated brain activity measured with fMRI during a response-inhibition task in matched heavy- and light-alcohol-drinking college students. Participants were light (N=36) and heavy (N=56) drinkers, aged 18–20 years. We characterized blood oxygen level-dependent (BOLD) responses, while participants performed an fMRI Go/No-Go task to quantify inhibitory behavior and brain activity. Behaviorally, group performance differences were observed for Go correct-hit and No-Go false-alarm reaction times with increased reaction times in heavy compared with light drinkers. During fMRI No-Go correct rejections, light drinkers exhibited greater BOLD response than did heavy drinkers in left supplementary motor area (SMA), bilateral parietal lobule, right hippocampus, bilateral middle frontal gyrus, left superior temporal gyrus, and cingulate gyrus/anterior cingulate cortex (Brodmann area 24). Group differences in Go/No-Go-related regional activations correlated with alcohol- and impulsivity-related measures. These findings suggest that heavy alcohol drinkers may have dysfunction in brain regions underlying attention and response inhibition, leading to diminished abilities to suppress prepotent responding. The extent to which these tendencies relate to impulsive decision-making and behaviors in real-life settings and may guide intervention development warrants additional investigation. PMID:23670589

Is brain response to food rewards related to overeating? A test of the reward surfeit model of overeating in children.

PubMed

Adise, Shana; Geier, Charles F; Roberts, Nicole J; White, Corey N; Keller, Kathleen L

2018-06-08

The reward surfeit model of overeating suggests that heightened brain response to rewards contributes to overeating and subsequent weight gain. However, previous studies have not tested whether brain response to reward is associated with food intake, particularly during childhood, a period of dynamic development in reward and inhibitory control neurocircuitry. We conducted functional magnetic resonance imaging (fMRI) with 7-11-year-old children (n = 59; healthy weight, n = 31; overweight, n = 28; 54% female) while they played a modified card-guessing paradigm to examine blood-oxygen-level-dependent (BOLD) response to anticipating and winning rewards (food, money, neutral). Food intake was assessed at three separate meals that measured different facets of eating behavior: 1) typical consumption (baseline), 2) overindulgence (palatable buffet), and 3) eating in the absence of hunger (EAH). A priori regions of interest included regions implicated in both reward processing and inhibitory control. Multiple stepwise regressions were conducted to examine the relationship between intake and BOLD response to rewards. Corrected results showed that a greater BOLD response in the medial prefrontal cortex for anticipating food compared to money positively correlated with how much children ate at the baseline and palatable buffet meals. BOLD response in the dorsolateral prefrontal cortex for winning food compared to money was positively correlated with intake at the palatable buffet meal and EAH. All aforementioned relationships were independent of child weight status. Findings support the reward surfeit model by showing that increased brain response to food compared to money rewards positively correlates with laboratory measures of food intake in children. Copyright © 2018. Published by Elsevier Ltd.

Localization of deformed wing virus (DWV) in the brains of the honeybee, Apis mellifera Linnaeus.

PubMed

Shah, Karan S; Evans, Elizabeth C; Pizzorno, Marie C

2009-10-30

Deformed wing virus (DWV) is a positive-strand RNA virus that infects European honeybees (Apis mellifera L.) and has been isolated from the brains of aggressive bees in Japan. DWV is known to be transmitted both vertically and horizontally between bees in a colony and can lead to both symptomatic and asymptomatic infections in bees. In environmentally stressful conditions, DWV can contribute to the demise of a honeybee colony. The purpose of the current study is to identify regions within the brains of honeybees where DWV replicates using in-situ hybridization. In-situ hybridizations were conducted with both sense and antisense probes on the brains of honeybees that were positive for DWV as measured by real-time RT-PCR. The visual neuropils demonstrated detectable levels of the DWV positive-strand genome. The mushroom bodies and antenna lobe neuropils also showed the presence of the viral genome. Weaker staining with the sense probe in the same regions demonstrates that the antigenome is also present and that the virus is actively replicating in these regions of the brain. These results demonstrate that in bees infected with DWV the virus is replicating in critical regions of the brain, including the neuropils responsible for vision and olfaction. Therefore DWV infection of the brain could adversely affect critical sensory functions and alter normal bee behavior.

Frequent ice cream consumption is associated with reduced striatal response to receipt of an ice cream–based milkshake123

PubMed Central

Stice, Eric

2012-01-01

Background: Weight gain leads to reduced reward-region responsivity to energy-dense food receipt, and consumption of an energy-dense diet compared with an isocaloric, low-energy-density diet leads to reduced dopamine receptors. Furthermore, phasic dopamine signaling to palatable food receipt decreases after repeated intake of that food, which collectively suggests that frequent intake of an energy-dense food may reduce striatal response to receipt of that food. Objective: We tested the hypothesis that frequent ice cream consumption would be associated with reduced activation in reward-related brain regions (eg, striatum) in response to receipt of an ice cream–based milkshake and examined the influence of adipose tissue and the specificity of this relation. Design: Healthy-weight adolescents (n = 151) underwent fMRI during receipt of a milkshake and during receipt of a tasteless solution. Percentage body fat, reported food intake, and food craving and liking were assessed. Results: Milkshake receipt robustly activated the striatal regions, yet frequent ice cream consumption was associated with a reduced response to milkshake receipt in these reward-related brain regions. Percentage body fat, total energy intake, percentage of energy from fat and sugar, and intake of other energy-dense foods were not related to the neural response to milkshake receipt. Conclusions: Our results provide novel evidence that frequent consumption of ice cream, independent of body fat, is related to a reduction in reward-region responsivity in humans, paralleling the tolerance observed in drug addiction. Data also imply that intake of a particular energy-dense food results in attenuated reward-region responsivity specifically to that food, which suggests that sensory aspects of eating and reward learning may drive the specificity. PMID:22338036

Frequent ice cream consumption is associated with reduced striatal response to receipt of an ice cream-based milkshake.

PubMed

Burger, Kyle S; Stice, Eric

2012-04-01

Weight gain leads to reduced reward-region responsivity to energy-dense food receipt, and consumption of an energy-dense diet compared with an isocaloric, low-energy-density diet leads to reduced dopamine receptors. Furthermore, phasic dopamine signaling to palatable food receipt decreases after repeated intake of that food, which collectively suggests that frequent intake of an energy-dense food may reduce striatal response to receipt of that food. We tested the hypothesis that frequent ice cream consumption would be associated with reduced activation in reward-related brain regions (eg, striatum) in response to receipt of an ice cream-based milkshake and examined the influence of adipose tissue and the specificity of this relation. Healthy-weight adolescents (n = 151) underwent fMRI during receipt of a milkshake and during receipt of a tasteless solution. Percentage body fat, reported food intake, and food craving and liking were assessed. Milkshake receipt robustly activated the striatal regions, yet frequent ice cream consumption was associated with a reduced response to milkshake receipt in these reward-related brain regions. Percentage body fat, total energy intake, percentage of energy from fat and sugar, and intake of other energy-dense foods were not related to the neural response to milkshake receipt. Our results provide novel evidence that frequent consumption of ice cream, independent of body fat, is related to a reduction in reward-region responsivity in humans, paralleling the tolerance observed in drug addiction. Data also imply that intake of a particular energy-dense food results in attenuated reward-region responsivity specifically to that food, which suggests that sensory aspects of eating and reward learning may drive the specificity.

Brain Response to Working Memory Over Three Years of Adolescence: Influence of Initiating Heavy Drinking

PubMed Central

Squeglia, Lindsay M.; Pulido, Carmen; Wetherill, Reagan R.; Jacobus, Joanna; Brown, Gregory G.; Tapert, Susan F.

2012-01-01

Objective: Many adolescents engage in heavy alcohol use. The aim of this study was to disentangle whether brain abnormalities seen in adolescent heavy drinkers are a consequence of heavy drinking, a preexisting risk factor for initiation of alcohol use, or both. Method: Study 1 used cross-sectional functional magnetic resonance imaging (fMRI) visual working-memory (VWM) data from 15- to 19-year-olds (20 heavy drinkers, 20 controls) to identify brain regions affected by heavy adolescent alcohol use. Study 2 used longitudinal fMRI VWM data from 12- to 16-year-olds imaged before the onset of drinking and imaged again on the same scanner approximately 3 years later. Those who had transitioned into heavy drinking (n = 20) were matched to continuous nondrinkers (n = 20) on baseline alcohol risk and developmental factors (N = 40; 80 scans). Results: Study 1 found that heavy drinkers exhibited more frontal and parietal but less occipital activation than controls, defining the regions of interest for Study 2. In Study 2, adolescents who later transitioned into heavy drinking showed less fMRI response contrast at baseline than continuous nondrinkers, which increased after the onset of heavy drinking, in frontal (1,431 μL, p = .003; η2 = .19) and parietal (810 μL, p = .005; η2 = .23) regions, as in Study 1. Lower baseline activation in the frontal and parietal regions predicted subsequent substance use, more so than commonly observed predictors of youth drinking (p < .05). Conclusions: Adolescents who initiated heavy drinking showed different brain activation before the onset of drinking, then less efficient information processing after high-dose alcohol use started. This suggests neural response patterns that could be risk factors for future substance use and also supports prior neuropsychological reports indicating that initiating heavy episodic drinking in adolescence may be followed by subtle alterations in brain functioning. PMID:22846239

The role of the Drosophila lateral horn in olfactory information processing and behavioral response.

PubMed

Schultzhaus, Janna N; Saleem, Sehresh; Iftikhar, Hina; Carney, Ginger E

2017-04-01

Animals must rapidly and accurately process environmental information to produce the correct behavioral responses. Reactions to previously encountered as well as to novel but biologically important stimuli are equally important, and one understudied region in the insect brain plays a role in processing both types of stimuli. The lateral horn is a higher order processing center that mainly processes olfactory information and is linked via olfactory projection neurons to another higher order learning center, the mushroom body. This review focuses on the lateral horn of Drosophila where most functional studies have been performed. We discuss connectivity between the primary olfactory center, the antennal lobe, and the lateral horn and mushroom body. We also present evidence for the lateral horn playing roles in innate behavioral responses by encoding biological valence to novel odor cues and in learned responses to previously encountered odors by modulating neural activity within the mushroom body. We describe how these processes contribute to acceptance or avoidance of appropriate or inappropriate mates and food, as well as the identification of predators. The lateral horn is a sexually dimorphic and plastic region of the brain that modulates other regions of the brain to ensure that insects produce rapid and effective behavioral responses to both novel and learned stimuli, yet multiple gaps exist in our knowledge of this important center. We anticipate that future studies on olfactory processing, learning, and innate behavioral responses will include the lateral horn in their examinations, leading to a more comprehensive understanding of olfactory information relay and resulting behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Brain stimulation-induced neuroplasticity underlying therapeutic response in phantom sounds.

PubMed

Poeppl, Timm B; Langguth, Berthold; Lehner, Astrid; Frodl, Thomas; Rupprecht, Rainer; Kreuzer, Peter M; Landgrebe, Michael; Schecklmann, Martin

2018-01-01

Noninvasive brain stimulation can modify phantom sounds for longer periods by modulating neural activity and putatively inducing regional neuroplastic changes. However, treatment response is limited and there are no good demographic or clinical predictors for treatment outcome. We used state-of-the-art voxel-based morphometry (VBM) to investigate whether transcranial magnetic stimulation-induced neuroplasticity determines therapeutic outcome. Sixty subjects chronically experiencing phantom sounds (i.e., tinnitus) received repetitive transcranial magnetic stimulation (rTMS) of left dorsolateral prefrontal and temporal cortex according to a protocol that has been shown to yield a significantly higher number of treatment responders than sham stimulation and previous stimulation protocols. Structural magnetic resonance imaging was performed before and after rTMS. In VBM whole-brain analyses (P < 0.05, FWE corrected), we assessed longitudinal gray matter changes as well as structural connectivity between the ensuing regions. We observed longitudinal mesoscopic gray matter changes of left dorsolateral prefontal (DLPFC), left operculo-insular, and right inferior temporal cortex (ITC) in responders (N = 22) but not nonresponders (N = 38), as indicated by a group × time interaction and post-hoc tests. These results were neither influenced by age, sex, hearing loss nor by tinnitus laterality, duration, and severity at baseline. Furthermore, we found robust DLPFC-insula and insula-ITC connectivity in responders, while only relatively weak DLPFC-insula connectivity and no insula-ITC connectivity could be demonstrated in nonresponders. Our results reinforce the implication of nonauditory brain regions in phantom sounds and suggest the dependence of therapeutic response on their neuroplastic capabilities. The latter in turn may depend on (differences in) their individual structural connectivity. Hum Brain Mapp 39:554-562, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Diffuse traumatic brain injury initially attenuates and later expands activation of the rat somatosensory whisker circuit concomitant with neuroplastic responses.

PubMed

Hall, Kelley D; Lifshitz, Jonathan

2010-04-06

Traumatic brain injury can initiate an array of chronic neurological deficits, effecting executive function, language and sensorimotor integration. Mechanical forces produce the diffuse pathology that disrupts neural circuit activation across vulnerable brain regions. The present manuscript explores the hypothesis that the extent of functional activation of brain-injured circuits is a consequence of initial disruption and consequent reorganization. In the rat, enduring sensory sensitivity to whisker stimulation directs regional analysis to the whisker barrel circuit. Adult, male rats were subjected to midline fluid percussion brain or sham injury and evaluated between 1day and 42days post-injury. Whisker somatosensory regions of the cortex and thalamus maintained cellular composition as visualized by Nissl stain. Within the first week post-injury, quantitatively less cFos activation was elicited by whisker stimulation, potentially due to axotomy within and surrounding the whisker circuit as visualized by amyloid precursor protein immunohistochemistry. Over six weeks post-injury, cFos activation after whisker stimulation showed a significant linear correlation with time in the cortex (r(2)=0.545; p=0.015), non-significant correlation in the thalamus (r(2)=0.326) and U-shaped correlation in the dentate gyrus (r(2)=0.831), all eventually exceeding sham levels. Ongoing neuroplastic responses in the cortex are evidenced by accumulating growth associated protein and synaptophysin gene expression. In the thalamus, the delayed restoration of plasticity markers may explain the broad distribution of neuronal activation extending into the striatum and hippocampus with whisker stimulation. The sprouting of diffuse-injured circuits into diffuse-injured tissue likely establishes maladaptive circuits responsible for behavioral morbidity. Therapeutic interventions to promote adaptive circuit restructuring may mitigate post-traumatic morbidity. Copyright 2010 Elsevier B.V. All rights reserved.

Transduction of Nonhuman Primate Brain with Adeno-Associated Virus Serotype 1: Vector Trafficking and Immune Response

PubMed Central

Forsayeth, John; Mirek, Hanna; Munson, Keith; Bringas, John; Pivirotto, Phil; McBride, Jodi L; Davidson, Beverly L.; Bankiewicz, Krystof S.

2009-01-01

Abstract We used convection-enhanced delivery (CED) to characterize gene delivery mediated by adeno-associated virus type 1 (AAV1) by tracking expression of hrGFP (humanized green fluorescent protein from Renilla reniformis) into the striatum, basal forebrain, and corona radiata of monkey brain. Four cynomolgus monkeys received single infusions into corona radiata, putamen, and caudate. The other group (n = 4) received infusions into basal forebrain. Thirty days after infusion animals were killed and their brains were processed for immunohisto-chemical evaluation. Volumetric analysis of GFP-positive brain areas was performed. AAV1-hrGFP infusions resulted in approximately 550, 700, and 73 mm3 coverage after infusion into corona radiata, striatum, and basal forebrain, respectively. Aside from targeted regions, other brain structures also showed GFP signal (internal and external globus pallidus, subthalamic nucleus), supporting the idea that AAV1 is actively trafficked to regions distal from the infusion site. In addition to neuronal transduction, a significant nonneuronal cell population was transduced by AAV1 vector; for example, oligodendrocytes in corona radiata and astrocytes in the striatum. We observed a strong humoral and cell-mediated response against AAV1-hrGFP in transduced monkeys irrespective of the anatomic location of the infusion, as evidenced by induction of circulating anti-AAV1 and anti-hrGFP antibodies, as well as infiltration of CD4+ lymphocytes and upregulation of MHC-II in regions infused with vector. We conclude that transduction of antigen-presenting cells within the CNS is a likely cause of this response and that caution is warranted when foreign transgenes are used as reporters in gene therapy studies with vectors with broader tropism than AAV2. PMID:19292604

Infants and adults have similar regional functional brain organization for the perception of emotions.

PubMed

Rotem-Kohavi, N; Oberlander, T F; Virji-Babul, N

2017-05-22

An infant's ability to perceive emotional facial expressions is critical for developing social skills. Infants are tuned to faces from early in life, however the functional organization of the brain that supports the processing of emotional faces in infants is still not well understood. We recorded electroencephalography (EEG) brain responses in 8-10 month old infants and adults and applied graph theory analysis on the functional connections to compare the network organization at the global and the regional levels underlying the perception of negative and positive dynamic facial expressions (happiness and sadness). We first show that processing of dynamic emotional faces occurs across multiple brain regions in both infants and adults. Across all brain regions, at the global level, network density was higher in the infant group in comparison with adults suggesting that the overall brain organization in relation to emotion perception is still immature in infancy. In contrast, at the regional levels, the functional characteristics of the frontal and parietal nodes were similar between infants and adults, suggesting that functional regional specialization for emotion perception is already established at this age. In addition, in both groups the occipital, parietal and temporal nodes appear to have the strongest influence on information flow within the network. These results suggest that while the global organization for the emotion perception of sad and happy emotions is still under development, the basic functional network organization at the regional level is already in place early in infancy. Copyright © 2017 Elsevier B.V. All rights reserved.

Differences in the time course of dopaminergic supersensitivity following chronic administration of haloperidol, molindone, or sulpiride.

PubMed

Prosser, E S; Pruthi, R; Csernansky, J G

1989-01-01

The onset and persistence of changes in 3H-spiroperidol binding to dopamine (DA) D2 receptors were examined in rat mesolimbic and striatal brain regions following daily administration of haloperidol, molindone, or sulpiride for 3, 7, 14, or 28 days. Neuroleptic dose equivalencies were determined by inhibition of 3H-spiroperidol in vivo binding in several rat brain regions. Changes in locomotor and stereotyped responses to the specific DA D2 agonist quinpirole were examined 3 days after the last treatment dose. Haloperidol or molindone administration increased mean stereotypy scores and striatal DA D2 receptor densities throughout the 28-day treatment period. In contrast, mesolimbic DA D2 receptor densities were transiently increased and returned to control values, after 28 days of haloperidol or molindone treatment. Sulpiride treatment increased mean stereotypy scores and striatal Bmax values, but had no effect on locomotion or mesolimbic dopamine receptor density. Additionally, the magnitude of change in the various measures of brain DA function varied among the three neuroleptic treatment groups. Results from this study suggest that mesolimbic and striatal brain regions differ in their response to long-term neuroleptic administration and that drug choice may influence the magnitude of neuroleptic-induced dopaminergic supersensitivity.

Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in rat brain slices.

PubMed

Watanabe, T; Morimoto, A; Murakami, N

1987-06-01

We investigated the effects of endogenous pyrogen and prostaglandin E2 (PGE2) on the preoptic and anterior hypothalamic (POAH) neurons using brain slice preparations from the rat. Partially purified endogenous pyrogen did not change the activities of most of the neurons in the POAH region when applied locally through a micropipette attached to the recording electrode in proximity to the neurons. This indicates that partially purified endogenous pyrogen does not act directly on the neuronal activity in the POAH region. The partially purified endogenous pyrogen, applied into a culture chamber containing a brain slice, facilitated the activities in 24% of the total neurons tested, regardless of the thermal specificity of the neurons. Moreover, PGE2 added to the culture chamber facilitated 48% of the warm-responsive, 33% of the cold-responsive, and 29% of the thermally insensitive neurons. The direction of change in neuronal activity induced by partially purified endogenous pyrogen appears to be almost the same as that induced by PGE2 when these substances were applied by perfusion to the same neuron in the culture chamber. These results suggest that partially purified pyrogen applied to the perfusate of the culture chamber stimulates some constituents of brain tissue to synthesize and release prostaglandin, which in turn affects the neuronal activity of the POAH region.

A Skew-t space-varying regression model for the spectral analysis of resting state brain activity.

PubMed

Ismail, Salimah; Sun, Wenqi; Nathoo, Farouk S; Babul, Arif; Moiseev, Alexader; Beg, Mirza Faisal; Virji-Babul, Naznin

2013-08-01

It is known that in many neurological disorders such as Down syndrome, main brain rhythms shift their frequencies slightly, and characterizing the spatial distribution of these shifts is of interest. This article reports on the development of a Skew-t mixed model for the spatial analysis of resting state brain activity in healthy controls and individuals with Down syndrome. Time series of oscillatory brain activity are recorded using magnetoencephalography, and spectral summaries are examined at multiple sensor locations across the scalp. We focus on the mean frequency of the power spectral density, and use space-varying regression to examine associations with age, gender and Down syndrome across several scalp regions. Spatial smoothing priors are incorporated based on a multivariate Markov random field, and the markedly non-Gaussian nature of the spectral response variable is accommodated by the use of a Skew-t distribution. A range of models representing different assumptions on the association structure and response distribution are examined, and we conduct model selection using the deviance information criterion. (1) Our analysis suggests region-specific differences between healthy controls and individuals with Down syndrome, particularly in the left and right temporal regions, and produces smoothed maps indicating the scalp topography of the estimated differences.

Affective and executive network processing associated with persuasive antidrug messages.

PubMed

Ramsay, Ian S; Yzer, Marco C; Luciana, Monica; Vohs, Kathleen D; MacDonald, Angus W

2013-07-01

Previous research has highlighted brain regions associated with socioemotional processes in persuasive message encoding, whereas cognitive models of persuasion suggest that executive brain areas may also be important. The current study aimed to identify lateral prefrontal brain areas associated with persuasive message viewing and understand how activity in these executive regions might interact with activity in the amygdala and medial pFC. Seventy adolescents were scanned using fMRI while they watched 10 strongly convincing antidrug public service announcements (PSAs), 10 weakly convincing antidrug PSAs, and 10 advertisements (ads) unrelated to drugs. Antidrug PSAs compared with nondrug ads more strongly elicited arousal-related activity in the amygdala and medial pFC. Within antidrug PSAs, those that were prerated as strongly persuasive versus weakly persuasive showed significant differences in arousal-related activity in executive processing areas of the lateral pFC. In support of the notion that persuasiveness involves both affective and executive processes, functional connectivity analyses showed greater coactivation between the lateral pFC and amygdala during PSAs known to be strongly (vs. weakly) convincing. These findings demonstrate that persuasive messages elicit activation in brain regions responsible for both emotional arousal and executive control and represent a crucial step toward a better understanding of the neural processes responsible for persuasion and subsequent behavior change.

The role of the GABAergic and dopaminergic systems in the brain response to an intragastric load of alcohol in conscious rats.

PubMed

Tsurugizawa, T; Uematsu, A; Uneyama, H; Torii, K

2010-12-01

The brain's response to ethanol intake has been extensively investigated using electrophysiological recordings, brain lesion techniques, and c-Fos immunoreactivity. However, few studies have investigated this phenomenon using functional magnetic resonance imaging (fMRI). In the present study, we used fMRI to investigate the blood oxygenation level-dependent (BOLD) signal response to an intragastric (IG) load of ethanol in conscious, ethanol-naive rats. An intragastrically infused 10% ethanol solution induced a significant decrease in the intensity of the BOLD signal in several regions of the brain, including the bilateral amygdala (AMG), nucleus accumbens (NAc), hippocampus, ventral pallidum, insular cortex, and cingulate cortex, and an increase in the BOLD signal in the ventral tegmental area (VTA) and hypothalamic regions. Treatment with bicuculline, which is an antagonist of the gamma-aminobutyric acid A (GABA(A)) receptor, increased the BOLD signal intensity in the regions that had shown decreases in the BOLD signal after the IG infusion of 10% ethanol solution, but it did not affect the BOLD signal increase in the hypothalamus. Treatment with SCH39166, which is an antagonist of D1-like receptors, eliminated the increase in the BOLD signal intensity in the hypothalamic areas but did not affect the BOLD signal decrease following the 10% ethanol infusion. These results indicate that an IG load of ethanol caused both a GABA(A) receptor-mediated BOLD decrease in the limbic system and the cortex and a D1-like receptor-mediated BOLD increase in the hypothalamic regions in ethanol-naive rats. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Synaptic Modifications in the Medial Prefrontal Cortex in Susceptibility and Resilience to Stress

PubMed Central

Wang, Minghui; Perova, Zinaida; Arenkiel, Benjamin R.

2014-01-01

When facing stress, most individuals are resilient whereas others are prone to developing mood disorders. The brain mechanisms underlying such divergent behavioral responses remain unclear. Here we used the learned helplessness procedure in mice to examine the role of the medial prefrontal cortex (mPFC), a brain region highly implicated in both clinical and animal models of depression, in adaptive and maladaptive behavioral responses to stress. We found that uncontrollable and inescapable stress induced behavioral state-dependent changes in the excitatory synapses onto a subset of mPFC neurons: those that were activated during behavioral responses as indicated by their expression of the activity reporter c-Fos. Whereas synaptic potentiation was linked to learned helplessness, a depression-like behavior, synaptic weakening, was associated with resilience to stress. Notably, enhancing the activity of mPFC neurons using a chemical–genetic method was sufficient to convert the resilient behavior into helplessness. Our results provide direct evidence that mPFC dysfunction is linked to maladaptive behavioral responses to stress, and suggest that enhanced excitatory synaptic drive onto mPFC neurons may underlie the previously reported hyperactivity of this brain region in depression. PMID:24872553

The allostatic impact of chronic ethanol on gene expression: A genetic analysis of chronic intermittent ethanol treatment in the BXD cohort

PubMed Central

van der Vaart, Andrew D.; Wolstenholme, Jennifer T.; Smith, Maren L.; Harris, Guy M.; Lopez, Marcelo F.; Wolen, Aaron R.; Becker, Howard C.; Williams, Robert W.; Miles, Michael F.

2016-01-01

The transition from acute to chronic ethanol exposure leads to lasting behavioral and physiological changes such as increased consumption, dependence, and withdrawal. Changes in brain gene expression are hypothesized to underlie these adaptive responses to ethanol. Previous studies on acute ethanol identified genetic variation in brain gene expression networks and behavioral responses to ethanol across the BXD panel of recombinant inbred mice. In this work, we have performed the first joint genetic and genomic analysis of transcriptome shifts in response to chronic intermittent ethanol (CIE) by vapor chamber exposure in a BXD cohort. CIE treatment is known to produce significant and sustained changes in ethanol consumption with repeated cycles of ethanol vapor. Using Affymetrix microarray analysis of prefrontal cortex (PFC) and nucleus accumbens (NAC) RNA, we compared CIE expression responses to those seen following acute ethanol treatment, and to voluntary ethanol consumption. Gene expression changes in PFC and NAC after CIE overlapped significantly across brain regions and with previously published expression following acute ethanol. Genes highly modulated by CIE were enriched for specific biological processes including synaptic transmission, neuron ensheathment, intracellular signaling, and neuronal projection development. Expression quantitative trait locus (eQTL) analyses identified genomic loci associated with ethanol-induced transcriptional changes with largely distinct loci identified between brain regions. Correlating CIE-regulated genes to ethanol consumption data identified specific genes highly associated with variation in the increase in drinking seen with repeated cycles of CIE. In particular, multiple myelin-related genes were identified. Furthermore, genetic variance in or near dynamin3 (Dnm3) on Chr1 at ~164 Mb may have a major regulatory role in CIE-responsive gene expression. Dnm3 expression correlates significantly with ethanol consumption, is contained in a highly ranked functional group of CIE-regulated genes in the NAC, and has a cis-eQTL within a genomic region linked with multiple CIE-responsive genes. PMID:27838001

Selective attention to temporal features on nested time scales.

PubMed

Henry, Molly J; Herrmann, Björn; Obleser, Jonas

2015-02-01

Meaningful auditory stimuli such as speech and music often vary simultaneously along multiple time scales. Thus, listeners must selectively attend to, and selectively ignore, separate but intertwined temporal features. The current study aimed to identify and characterize the neural network specifically involved in this feature-selective attention to time. We used a novel paradigm where listeners judged either the duration or modulation rate of auditory stimuli, and in which the stimulation, working memory demands, response requirements, and task difficulty were held constant. A first analysis identified all brain regions where individual brain activation patterns were correlated with individual behavioral performance patterns, which thus supported temporal judgments generically. A second analysis then isolated those brain regions that specifically regulated selective attention to temporal features: Neural responses in a bilateral fronto-parietal network including insular cortex and basal ganglia decreased with degree of change of the attended temporal feature. Critically, response patterns in these regions were inverted when the task required selectively ignoring this feature. The results demonstrate how the neural analysis of complex acoustic stimuli with multiple temporal features depends on a fronto-parietal network that simultaneously regulates the selective gain for attended and ignored temporal features. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Listening to urban soundscapes: Physiological validity of perceptual dimensions.

PubMed

Irwin, Amy; Hall, Deborah A; Peters, Andrew; Plack, Christopher J

2011-02-01

Predominantly, the impact of environmental noise is measured using sound level, ignoring the influence of other factors on subjective experience. The present study tested physiological responses to natural urban soundscapes, using functional magnetic resonance imaging and vector cardiogram. City-based recordings were matched in overall sound level (71 decibel A-weighted scale), but differed on ratings of pleasantness and vibrancy. Listening to soundscapes evoked significant activity in a number of auditory brain regions. Compared with soundscapes that evoked no (neutral) emotional response, those evoking a pleasant or unpleasant emotional response engaged an additional neural circuit including the right amygdala. Ratings of vibrancy had little effect overall, and brain responses were more sensitive to pleasantness than was heart rate. A novel finding is that urban soundscapes with similar loudness can have dramatically different effects on the brain's response to the environment. Copyright © 2010 Society for Psychophysiological Research.

Compensatory brain activation in children with attention deficit/hyperactivity disorder during a simplified Go/No-go task.

PubMed

Ma, Jun; Lei, Du; Jin, Xingming; Du, Xiaoxia; Jiang, Fan; Li, Fei; Zhang, Yiwen; Shen, Xiaoming

2012-05-01

Given that a number of recent studies have shown attenuated brain activation in prefrontal regions in children with ADHD, it has been recognized as a disorder in executive function. However, fewer studies have focused exclusively on the compensatory brain activation in ADHD. The present study objective was to investigate the compensatory brain activation patterns during response inhibition (RI) processing in ADHD children. In this study, 15 ADHD children and 15 sex-, age-, and IQ-matched control children were scanned with a 3-T MRI equipment while performing a simplified letter Go/No-go task. The results showed more brain activation in the ADHD group compared with the control group, whereas the accuracy and reaction time of behavioral performance were the same. Children with ADHD did not activate the normal RI brain circuits, which are thought to be predominantly located in the right middle/inferior frontal gyrus (BA46/44), right inferior parietal regions (BA40), and pre-SMA(BA6), but instead, activated brain regions, such as the left inferior frontal cortex, the right inferior temporal cortex, the right precentral gyrus, the left postcentral gyrus, the inferior occipital cortex, the middle occipital cortex, the right calcarine, the right hippocampus, the right midbrain, and the cerebellum. Our conclusion is that children with ADHD tend to compensatorily use more posterior and diffusive brain regions to sustain normal RI function. © Springer-Verlag 2011

Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli

PubMed Central

Field, Brent A.; Buck, Cara L.; McClure, Samuel M.; Nystrom, Leigh E.; Kahneman, Daniel; Cohen, Jonathan D.

2015-01-01

Studies of subjective well-being have conventionally relied upon self-report, which directs subjects’ attention to their emotional experiences. This method presumes that attention itself does not influence emotional processes, which could bias sampling. We tested whether attention influences experienced utility (the moment-by-moment experience of pleasure) by using functional magnetic resonance imaging (fMRI) to measure the activity of brain systems thought to represent hedonic value while manipulating attentional load. Subjects received appetitive or aversive solutions orally while alternatively executing a low or high attentional load task. Brain regions associated with hedonic processing, including the ventral striatum, showed a response to both juice and quinine. This response decreased during the high-load task relative to the low-load task. Thus, attentional allocation may influence experienced utility by modulating (either directly or indirectly) the activity of brain mechanisms thought to represent hedonic value. PMID:26158468

Regulation of body temperature in the blue-tongued lizard.

PubMed

Hammel, H T; Caldwell, F T; Abrams, R M

1967-06-02

Lizards (Tiliqua scincoides) regulated their internal body temperature by moving back and forth between 15 degrees and 45 degrees C environments to maintain colonic and brain temperatures between 30 degrees and 37 degrees C. A pair of thermodes were implanted across the preoptic region of the brain stem, and a reentrant tube for a thermocouple was implanted in the brain stem. Heating the brain stem to 41 degrees C activated the exit response from the hot environment at a colonic temperature 1 degrees to 2 degrees C lower than normal, whereas cooling the brain stem to 25 degrees C delayed the exit from the hot environment until the colonic temperature was 1 degrees to 2 degrees C higher than normal. The behavioral thermoregulatory responses of this ectotherm appear to be activated by a combination of hypothalamic and other body temperatures.

A Window into the Brain: Advances in Psychiatric fMRI

PubMed Central

Zhan, Xiaoyan

2015-01-01

Functional magnetic resonance imaging (fMRI) plays a key role in modern psychiatric research. It provides a means to assay differences in brain systems that underlie psychiatric illness, treatment response, and properties of brain structure and function that convey risk factor for mental diseases. Here we review recent advances in fMRI methods in general use and progress made in understanding the neural basis of mental illness. Drawing on concepts and findings from psychiatric fMRI, we propose that mental illness may not be associated with abnormalities in specific local regions but rather corresponds to variation in the overall organization of functional communication throughout the brain network. Future research may need to integrate neuroimaging information drawn from different analysis methods and delineate spatial and temporal patterns of brain responses that are specific to certain types of psychiatric disorders. PMID:26413531

A comparison of functional magnetic resonance imaging findings in children with and without a history of early exposure to general anesthesia.

PubMed

Taghon, Thomas A; Masunga, Abigail N; Small, Robert H; Kashou, Nasser H

2015-03-01

Functional magnetic resonance imaging (fMRI) has been used to evaluate the long-term consequences of early exposure to neurotoxic agents. fMRI shows that different patterns of brain activation occur in ethanol-exposed subjects performing a go/no-go response inhibition task. Pharmacologically, ethanol and general anesthetics have similar receptor-level activity in the brain. This study utilizes fMRI to examine brain activation patterns in children exposed to general anesthesia and surgery during early brain development. After obtaining Nationwide Children's Hospital IRB approval, a surgical database was utilized to identify children aged 10-17 years with a history of at least 1 h of exposure to general anesthetics and surgery when they were between 0 and 24 months of age. Age- and gender-matched children without anesthesia exposure were recruited as a control group. All subjects were scanned while being presented with a go/no-go response inhibition task. Reaction time and accuracy data were acquired, and the blood-oxygen-level-dependent (BOLD) fMRI signal was measured as a biomarker for regional neuronal activity. There were no differences in terms of performance accuracy and response time. The analysis did not reveal any significant activation differences in the primary region of interest (prefrontal cortex and caudate nucleus); however, activation differences were seen in other structures, including the cerebellum, cingulate gyrus, and paracentral lobule. Early anesthetic exposure and surgery did not affect accuracy, response time, or activation patterns in the primary region of interest during performance of the task. Intergroup differences in activation patterns in other areas of the brain were observed, and the significance of these findings is unknown. fMRI appears to be a useful tool in evaluating the long-term effects of early exposure to general anesthesia. © 2015 John Wiley & Sons Ltd.

Processing of targets in smooth or apparent motion along the vertical in the human brain: an fMRI study.

PubMed

Maffei, Vincenzo; Macaluso, Emiliano; Indovina, Iole; Orban, Guy; Lacquaniti, Francesco

2010-01-01

Neural substrates for processing constant speed visual motion have been extensively studied. Less is known about the brain activity patterns when the target speed changes continuously, for instance under the influence of gravity. Using functional MRI (fMRI), here we compared brain responses to accelerating/decelerating targets with the responses to constant speed targets. The target could move along the vertical under gravity (1g), under reversed gravity (-1g), or at constant speed (0g). In the first experiment, subjects observed targets moving in smooth motion and responded to a GO signal delivered at a random time after target arrival. As expected, we found that the timing of the motor responses did not depend significantly on the specific motion law. Therefore brain activity in the contrast between different motion laws was not related to motor timing responses. Average BOLD signals were significantly greater for 1g targets than either 0g or -1g targets in a distributed network including bilateral insulae, left lingual gyrus, and brain stem. Moreover, in these regions, the mean activity decreased monotonically from 1g to 0g and to -1g. In the second experiment, subjects intercepted 1g, 0g, and -1g targets either in smooth motion (RM) or in long-range apparent motion (LAM). We found that the sites in the right insula and left lingual gyrus, which were selectively engaged by 1g targets in the first experiment, were also significantly more active during 1g trials than during -1g trials both in RM and LAM. The activity in 0g trials was again intermediate between that in 1g trials and that in -1g trials. Therefore in these regions the global activity modulation with the law of vertical motion appears to hold for both RM and LAM. Instead, a region in the inferior parietal lobule showed a preference for visual gravitational motion only in LAM but not RM.

Inter-subject synchronization of brain responses during natural music listening

PubMed Central

Abrams, Daniel A.; Ryali, Srikanth; Chen, Tianwen; Chordia, Parag; Khouzam, Amirah; Levitin, Daniel J.; Menon, Vinod

2015-01-01

Music is a cultural universal and a rich part of the human experience. However, little is known about common brain systems that support the processing and integration of extended, naturalistic ‘real-world’ music stimuli. We examined this question by presenting extended excerpts of symphonic music, and two pseudomusical stimuli in which the temporal and spectral structure of the Natural Music condition were disrupted, to non-musician participants undergoing functional brain imaging and analysing synchronized spatiotemporal activity patterns between listeners. We found that music synchronizes brain responses across listeners in bilateral auditory midbrain and thalamus, primary auditory and auditory association cortex, right-lateralized structures in frontal and parietal cortex, and motor planning regions of the brain. These effects were greater for natural music compared to the pseudo-musical control conditions. Remarkably, inter-subject synchronization in the inferior colliculus and medial geniculate nucleus was also greater for the natural music condition, indicating that synchronization at these early stages of auditory processing is not simply driven by spectro-temporal features of the stimulus. Increased synchronization during music listening was also evident in a right-hemisphere fronto-parietal attention network and bilateral cortical regions involved in motor planning. While these brain structures have previously been implicated in various aspects of musical processing, our results are the first to show that these regions track structural elements of a musical stimulus over extended time periods lasting minutes. Our results show that a hierarchical distributed network is synchronized between individuals during the processing of extended musical sequences, and provide new insight into the temporal integration of complex and biologically salient auditory sequences. PMID:23578016

Decoding the neural signatures of emotions expressed through sound.

PubMed

Sachs, Matthew E; Habibi, Assal; Damasio, Antonio; Kaplan, Jonas T

2018-07-01

Effective social functioning relies in part on the ability to identify emotions from auditory stimuli and respond appropriately. Previous studies have uncovered brain regions engaged by the affective information conveyed by sound. But some of the acoustical properties of sounds that express certain emotions vary remarkably with the instrument used to produce them, for example the human voice or a violin. Do these brain regions respond in the same way to different emotions regardless of the sound source? To address this question, we had participants (N = 38, 20 females) listen to brief audio excerpts produced by the violin, clarinet, and human voice, each conveying one of three target emotions-happiness, sadness, and fear-while brain activity was measured with fMRI. We used multivoxel pattern analysis to test whether emotion-specific neural responses to the voice could predict emotion-specific neural responses to musical instruments and vice-versa. A whole-brain searchlight analysis revealed that patterns of activity within the primary and secondary auditory cortex, posterior insula, and parietal operculum were predictive of the affective content of sound both within and across instruments. Furthermore, classification accuracy within the anterior insula was correlated with behavioral measures of empathy. The findings suggest that these brain regions carry emotion-specific patterns that generalize across sounds with different acoustical properties. Also, individuals with greater empathic ability have more distinct neural patterns related to perceiving emotions. These results extend previous knowledge regarding how the human brain extracts emotional meaning from auditory stimuli and enables us to understand and connect with others effectively. Copyright © 2018 Elsevier Inc. All rights reserved.

Common resting brain dynamics indicate a possible mechanism underlying zolpidem response in severe brain injury

PubMed Central

Williams, Shawniqua T; Conte, Mary M; Goldfine, Andrew M; Noirhomme, Quentin; Gosseries, Olivia; Thonnard, Marie; Beattie, Bradley; Hersh, Jennifer; Katz, Douglas I; Victor, Jonathan D; Laureys, Steven; Schiff, Nicholas D

2013-01-01

Zolpidem produces paradoxical recovery of speech, cognitive and motor functions in select subjects with severe brain injury but underlying mechanisms remain unknown. In three diverse patients with known zolpidem responses we identify a distinctive pattern of EEG dynamics that suggests a mechanistic model. In the absence of zolpidem, all subjects show a strong low frequency oscillatory peak ∼6–10 Hz in the EEG power spectrum most prominent over frontocentral regions and with high coherence (∼0.7–0.8) within and between hemispheres. Zolpidem administration sharply reduces EEG power and coherence at these low frequencies. The ∼6–10 Hz activity is proposed to arise from intrinsic membrane properties of pyramidal neurons that are passively entrained across the cortex by locally-generated spontaneous activity. Activation by zolpidem is proposed to arise from a combination of initial direct drug effects on cortical, striatal, and thalamic populations and further activation of underactive brain regions induced by restoration of cognitively-mediated behaviors. DOI: http://dx.doi.org/10.7554/eLife.01157.001 PMID:24252875

Atrophy of spared gray matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke.

PubMed

Gauthier, Lynne V; Taub, Edward; Mark, Victor W; Barghi, Ameen; Uswatte, Gitendra

2012-02-01

Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery. Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy. Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke.

Atrophy of spared grey matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke

PubMed Central

Gauthier, Lynne V.; Taub, Edward; Mark, Victor W.; Barghi, Ameen; Uswatte, Gitendra

2011-01-01

Background and Purpose Although the motor deficit following stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to Constraint-Induced Movement therapy (CI therapy) in chronic stroke patients may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Methods Voxel-based morphometry (VBM) analysis was performed on MRI scans from 80 chronic stroke patients to investigate whether variations in grey matter density were correlated with extent of residual motor impairment or with CI therapy-induced motor recovery. Results Decreased grey matter density in non-infarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced grey matter density in multiple remote brain regions predicted a lesser extent of motor improvement from CI therapy. Conclusions Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke. PMID:22096036

Mechanical characterization of human brain tissue.

PubMed

Budday, S; Sommer, G; Birkl, C; Langkammer, C; Haybaeck, J; Kohnert, J; Bauer, M; Paulsen, F; Steinmann, P; Kuhl, E; Holzapfel, G A

2017-01-15

Mechanics are increasingly recognized to play an important role in modulating brain form and function. Computational simulations are a powerful tool to predict the mechanical behavior of the human brain in health and disease. The success of these simulations depends critically on the underlying constitutive model and on the reliable identification of its material parameters. Thus, there is an urgent need to thoroughly characterize the mechanical behavior of brain tissue and to identify mathematical models that capture the tissue response under arbitrary loading conditions. However, most constitutive models have only been calibrated for a single loading mode. Here, we perform a sequence of multiple loading modes on the same human brain specimen - simple shear in two orthogonal directions, compression, and tension - and characterize the loading-mode specific regional and directional behavior. We complement these three individual tests by combined multiaxial compression/tension-shear tests and discuss effects of conditioning and hysteresis. To explore to which extent the macrostructural response is a result of the underlying microstructural architecture, we supplement our biomechanical tests with diffusion tensor imaging and histology. We show that the heterogeneous microstructure leads to a regional but not directional dependence of the mechanical properties. Our experiments confirm that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry. Using our measurements, we compare the performance of five common constitutive models, neo-Hookean, Mooney-Rivlin, Demiray, Gent, and Ogden, and show that only the isotropic modified one-term Ogden model is capable of representing the hyperelastic behavior under combined shear, compression, and tension loadings: with a shear modulus of 0.4-1.4kPa and a negative nonlinearity parameter it captures the compression-tension asymmetry and the increase in shear stress under superimposed compression but not tension. Our results demonstrate that material parameters identified for a single loading mode fail to predict the response under arbitrary loading conditions. Our systematic characterization of human brain tissue will lead to more accurate computational simulations, which will allow us to determine criteria for injury, to develop smart protection systems, and to predict brain development and disease progression. There is a pressing need to characterize the mechanical behavior of human brain tissue under multiple loading conditions, and to identify constitutive models that are able to capture the tissue response under these conditions. We perform a sequence of experimental tests on the same brain specimen to characterize the regional and directional behavior, and we supplement our tests with DTI and histology to explore to which extent the macrostructural response is a result of the underlying microstructure. Results demonstrate that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry, and we show that the multiaxial data can best be captured by a modified version of the one-term Ogden model. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression.

PubMed

Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M; Pradhan, Kith; Henn, Fritz A; Shea, Stephen; Osten, Pavel; Li, Bo

2016-01-01

Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP - a marker of neuronal activation - in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing "helpless" behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing "resilient" behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.

Meta-analysis of functional brain imaging in specific phobia.

PubMed

Ipser, Jonathan C; Singh, Leesha; Stein, Dan J

2013-07-01

Although specific phobia is a prevalent anxiety disorder, evidence regarding its underlying functional neuroanatomy is inconsistent. A meta-analysis was undertaken to identify brain regions that were consistently responsive to phobic stimuli, and to characterize changes in brain activation following cognitive behavioral therapy (CBT). We searched the PubMed, SCOPUS and PsycINFO databases to identify positron emission tomography and functional magnetic resonance imaging studies comparing brain activation in specific phobia patients and healthy controls. Two raters independently extracted study data from all the eligible studies, and pooled coordinates from these studies using activation likelihood estimation, a quantitative meta-analytic technique. Resulting statistical parametric maps were compared between patients and healthy controls, in response to phobic versus fear-evoking stimuli, and before and after therapy. Thirteen studies were included, comprising 327 participants. Regions that were consistently activated in response to phobic stimuli included the left insula, amygdala, and globus pallidus. Compared to healthy controls, phobic subjects had increased activation in response to phobic stimuli in the left amygdala/globus pallidus, left insula, right thalamus (pulvinar), and cerebellum. Following exposure-based therapy widespread deactivation was observed in the right frontal cortex, limbic cortex, basal ganglia and cerebellum, with increased activation detected in the thalamus. Exposure to phobia-specific stimuli elicits brain activation that is consistent with current understandings of the neuroanatomy of fear conditioning and extinction. There is evidence that the effects of CBT in specific phobia may be mediated through the same underlying neurocircuitry. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Real-time photoacoustic imaging of rat deep brain: hemodynamic responses to hypoxia

NASA Astrophysics Data System (ADS)

Kawauchi, Satoko; Iwazaki, Hideaki; Ida, Taiichiro; Hosaka, Tomoya; Kawaguchi, Yasushi; Nawashiro, Hiroshi; Sato, Shunichi

2013-03-01

Hemodynamic responses of the brain to hypoxia or ischemia are one of the major interests in neurosurgery and neuroscience. In this study, we performed real-time transcutaneous PA imaging of the rat brain that was exposed to a hypoxic stress and investigated depth-resolved responses of the brain, including the hippocampus. A linear-array 8ch 10-MHz ultrasonic sensor (measurement length, 10 mm) was placed on the shaved scalp. Nanosecond, 570-nm and 595- nm light pulses were used to excite PA signals indicating cerebral blood volume (CBV) and blood deoxygenation, respectively. Under spontaneous respiration, inhalation gas was switched from air to nitrogen, and then reswitched to oxygen, during which real-time PA imaging was performed continuously. High-contrast PA signals were observed from the depth regions corresponding to the scalp, skull, cortex and hippocampus. After starting hypoxia, PA signals at 595 nm increased immediately in both the cortex and hippocampus for about 1.5 min, showing hemoglobin deoxygenation. On the other hand, PA signals at 570 nm coming from these regions did not increase in the early phase but started to increase at about 1.5 min after starting hypoxia, indicating reactive hyperemia to hypoxia. During hypoxia, PA signals coming from the scalp decreased transiently, which is presumably due to compensatory response in the peripheral tissue to preserve blood perfusion in the brain. The reoxygenation caused a gradual recovery of these PA signals. These findings demonstrate the usefulness of PA imaging for real-time, depth-resolved observation of cerebral hemodynamics.

Elevated cognitive control over reward processing in recovered female patients with anorexia nervosa.

PubMed

Ehrlich, Stefan; Geisler, Daniel; Ritschel, Franziska; King, Joseph A; Seidel, Maria; Boehm, Ilka; Breier, Marion; Clas, Sabine; Weiss, Jessika; Marxen, Michael; Smolka, Michael N; Roessner, Veit; Kroemer, Nils B

2015-09-01

Individuals with anorexia nervosa are thought to exert excessive self-control to inhibit primary drives. This study used functional MRI (fMRI) to interrogate interactions between the neural correlates of cognitive control and motivational processes in the brain reward system during the anticipation of monetary reward and reward-related feedback. In order to avoid confounding effects of undernutrition, we studied female participants recovered from anorexia nervosa and closely matched healthy female controls. The fMRI analysis (including node-to-node functional connectivity) followed a region of interest approach based on models of the brain reward system and cognitive control regions implicated in anorexia nervosa: the ventral striatum, medial orbitofrontal cortex (mOFC) and dorsolateral prefrontal cortex (DLPFC). We included 30 recovered patients and 30 controls in our study. There were no behavioural differences and no differences in hemodynamic responses of the ventral striatum and the mOFC in the 2 phases of the task. However, relative to controls, recovered patients showed elevated DLPFC activity during the anticipation phase, failed to deactivate this region during the feedback phase and displayed greater functional coupling between the DLPFC and mOFC. Recovered patients also had stronger associations than controls between anticipation-related DLPFC responses and instrumental responding. The results we obtained using monetary stimuli might not generalize to other forms of reward. Unaltered neural responses in ventral limbic reward networks but increased recruitment of and connectivity with lateral-frontal brain circuitry in recovered patients suggests an elevated degree of selfregulatory processes in response to rewarding stimuli. An imbalance between brain systems subserving bottom-up and top-down processes may be a trait marker of the disorder.

Cortical Representations of Symbols, Objects, and Faces Are Pruned Back during Early Childhood

PubMed Central

Pinel, Philippe; Dehaene, Stanislas; Pelphrey, Kevin A.

2011-01-01

Regions of human ventral extrastriate visual cortex develop specializations for natural categories (e.g., faces) and cultural artifacts (e.g., words). In adults, category-based specializations manifest as greater neural responses in visual regions of the brain (e.g., fusiform gyrus) to some categories over others. However, few studies have examined how these specializations originate in the brains of children. Moreover, it is as yet unknown whether the development of visual specializations hinges on “increases” in the response to the preferred categories, “decreases” in the responses to nonpreferred categories, or “both.” This question is relevant to a long-standing debate concerning whether neural development is driven by building up or pruning back representations. To explore these questions, we measured patterns of visual activity in 4-year-old children for 4 categories (faces, letters, numbers, and shoes) using functional magnetic resonance imaging. We report 2 key findings regarding the development of visual categories in the brain: 1) the categories “faces” and “symbols” doubly dissociate in the fusiform gyrus before children can read and 2) the development of category-specific responses in young children depends on cortical responses to nonpreferred categories that decrease as preferred category knowledge is acquired. PMID:20457691

Individual variation in the neural processes of motor decisions in the stop signal task: the influence of novelty seeking and harm avoidance personality traits.

PubMed

Hu, Jianping; Lee, Dianne; Hu, Sien; Zhang, Sheng; Chao, Herta; Li, Chiang-Shan R

2016-06-01

Personality traits contribute to variation in human behavior, including the propensity to take risk. Extant work targeted risk-taking processes with an explicit manipulation of reward, but it remains unclear whether personality traits influence simple decisions such as speeded versus delayed responses during cognitive control. We explored this issue in an fMRI study of the stop signal task, in which participants varied in response time trial by trial, speeding up and risking a stop error or slowing down to avoid errors. Regional brain activations to speeded versus delayed motor responses (risk-taking) were correlated to novelty seeking (NS), harm avoidance (HA) and reward dependence (RD), with age and gender as covariates, in a whole brain regression. At a corrected threshold, the results showed a positive correlation between NS and risk-taking responses in the dorsomedial prefrontal, bilateral orbitofrontal, and frontopolar cortex, and between HA and risk-taking responses in the parahippocampal gyrus and putamen. No regional activations varied with RD. These findings demonstrate that personality traits influence the neural processes of executive control beyond behavioral tasks that involve explicit monetary reward. The results also speak broadly to the importance of characterizing inter-subject variation in studies of cognition and brain functions.

Spatiotemporal oscillatory dynamics of visual selective attention during a flanker task.

PubMed

McDermott, Timothy J; Wiesman, Alex I; Proskovec, Amy L; Heinrichs-Graham, Elizabeth; Wilson, Tony W

2017-08-01

The flanker task is a test of visual selective attention that has been widely used to probe error monitoring, response conflict, and related constructs. However, to date, few studies have focused on the selective attention component of this task and imaged the underlying oscillatory dynamics serving task performance. In this study, 21 healthy adults successfully completed an arrow-based version of the Eriksen flanker task during magnetoencephalography (MEG). All MEG data were pre-processed and transformed into the time-frequency domain. Significant oscillatory brain responses were imaged using a beamforming approach, and voxel time series were extracted from the peak responses to identify the temporal dynamics. Across both congruent and incongruent flanker conditions, our results indicated robust decreases in alpha (9-12Hz) activity in medial and lateral occipital regions, bilateral parietal cortices, and cerebellar areas during task performance. In parallel, increases in theta (3-7Hz) oscillatory activity were detected in dorsal and ventral frontal regions, and the anterior cingulate. As per conditional effects, stronger alpha responses (i.e., greater desynchronization) were observed in parietal, occipital, and cerebellar cortices during incongruent relative to congruent trials, whereas the opposite pattern emerged for theta responses (i.e., synchronization) in the anterior cingulate, left dorsolateral prefrontal, and ventral prefrontal cortices. Interestingly, the peak latency of theta responses in these latter brain regions was significantly correlated with reaction time, and may partially explain the amplitude difference observed between congruent and incongruent trials. Lastly, whole-brain exploratory analyses implicated the frontal eye fields, right temporoparietal junction, and premotor cortices. These findings suggest that regions of both the dorsal and ventral attention networks contribute to visual selective attention processes during incongruent trials, and that such differential processes are transient and fully completed shortly after the behavioral response in most trials. Copyright © 2017 Elsevier Inc. All rights reserved.

Tau pathology does not affect experience-driven single-neuron and network-wide Arc/Arg3.1 responses.

PubMed

Rudinskiy, Nikita; Hawkes, Jonathan M; Wegmann, Susanne; Kuchibhotla, Kishore V; Muzikansky, Alona; Betensky, Rebecca A; Spires-Jones, Tara L; Hyman, Bradley T

2014-06-10

Intraneuronal neurofibrillary tangles (NFTs) - a characteristic pathological feature of Alzheimer's and several other neurodegenerative diseases - are considered a major target for drug development. Tangle load correlates well with the severity of cognitive symptoms and mouse models of tauopathy are behaviorally impaired. However, there is little evidence that NFTs directly impact physiological properties of host neurons. Here we used a transgenic mouse model of tauopathy to study how advanced tau pathology in different brain regions affects activity-driven expression of immediate-early gene Arc required for experience-dependent consolidation of long-term memories. We demonstrate in vivo that visual cortex neurons with tangles are as likely to express comparable amounts of Arc in response to structured visual stimulation as their neighbors without tangles. Probability of experience-dependent Arc response was not affected by tau tangles in both visual cortex and hippocampal pyramidal neurons as determined postmortem. Moreover, whole brain analysis showed that network-wide activity-driven Arc expression was not affected by tau pathology in any of the brain regions, including brain areas with the highest tangle load. Our findings suggest that intraneuronal NFTs do not affect signaling cascades leading to experience-dependent gene expression required for long-term synaptic plasticity.

Engagement of large-scale networks is related to individual differences in inhibitory control

PubMed Central

Congdon, Eliza; Mumford, Jeanette A.; Cohen, Jessica R.; Galvan, Adriana; Aron, Adam R.; Xue, Gui; Miller, Eric; Poldrack, Russell A.

2010-01-01

Understanding which brain regions regulate the execution, and suppression, of goal-directed behavior has implications for a number of areas of research. In particular, understanding which brain regions engaged during tasks requiring the execution and inhibition of a motor response provides insight into the mechanisms underlying individual differences in response inhibition ability. However, neuroimaging studies examing the relation between activation and stopping have been inconsistent regarding the direction of the relationship, and also regarding the anatomical location of regions that correlate with behavior. These limitations likely arise from the relatively low power of vox-elwise correlations with small sample sizes. Here, we pooled data over five separate fMRI studies of the Stop-signal task in order to obtain a sufficiently large sample size to robustly detect brain/behavior correlations. In addition, rather than performing mass univariate correlation analysis across all voxels, we increased statistical power by reducing the dimensionality of the data set using independent components analysis and then examined correlations between behavior and the resulting component scores. We found that components reflecting activity in regions thought to be involved in stopping were associated with better stopping ability, while activity in a default-mode network was associated with poorer stopping ability across individuals. These results clearly show a relationship between individual differences in stopping ability in specific activated networks, including regions known to be critical for the behavior. The results also highlight the usefulness of using dimensionality reduction to increase the power to detect brain/behavior correlations in individual differences research. PMID:20600962

Empathic control through coordinated interaction of amygdala, theory of mind and extended pain matrix brain regions.

PubMed

Bruneau, Emile G; Jacoby, Nir; Saxe, Rebecca

2015-07-01

Brain regions in the "pain matrix", can be activated by observing or reading about others in physical pain. In previous research, we found that reading stories about others' emotional suffering, by contrast, recruits a different group of brain regions mostly associated with thinking about others' minds. In the current study, we examined the neural circuits responsible for deliberately regulating empathic responses to others' pain and suffering. In Study 1, a sample of college-aged participants (n=18) read stories about physically painful and emotionally distressing events during functional magnetic resonance imaging (fMRI), while either actively empathizing with the main character or trying to remain objective. In Study 2, the same experiment was performed with professional social workers, who are chronically exposed to human suffering (n=21). Across both studies activity in the amygdala was associated with empathic regulation towards others' emotional pain, but not their physical pain. In addition, psychophysiological interaction (PPI) analysis and Granger causal modeling (GCM) showed that amygdala activity while reading about others' emotional pain was preceded by and positively coupled with activity in the theory of mind brain regions, and followed by and negatively coupled with activity in regions associated with physical pain and bodily sensations. Previous work has shown that the amygdala is critically involved in the deliberate control of self-focused distress - the current results extend the central importance of amygdala activity to the control of other-focused empathy, but only when considering others' emotional pain. Copyright © 2015 Elsevier Inc. All rights reserved.

Is neuroinflammation in the injured spinal cord different than in the brain? Examining intrinsic differences between the brain and spinal cord.

PubMed

Zhang, B; Gensel, J C

2014-08-01

The field of neuroimmunology is rapidly advancing. There is a growing appreciation for heterogeneity, both in inflammatory composition and region-specific inflammatory responses. This understanding underscores the importance of developing targeted immunomodulatory therapies for treating neurological disorders. Concerning neurotrauma, there is a dearth of publications directly comparing inflammatory responses in the brain and spinal cord after injury. The question therefore remains as to whether inflammatory cells responding to spinal cord vs. brain injury adopt similar functions and are therefore amenable to common therapies. In this review, we address this question while revisiting and modernizing the conclusions from publications that have directly compared inflammation across brain and spinal cord injuries. By examining molecular differences, anatomical variations, and inflammatory cell phenotypes between the injured brain and spinal cord, we provide insight into how neuroinflammation relates to neurotrauma and into fundamental differences between the brain and spinal cord. Copyright © 2014 Elsevier Inc. All rights reserved.

Thyroid hormone and cerebellar development.

PubMed

Anderson, Grant W

2008-01-01

Thyroid hormone (TH) plays a key role in mammalian brain development. The developing brain is sensitive to both TH deficiency and excess. Brain development in the absence of TH results in motor skill deficiencies and reduced intellectual development. These functional abnormalities can be attributed to maldevelopment of specific cell types and regions of the brain including the cerebellum. TH functions at the molecular level by regulating gene transcription. Therefore, understanding how TH regulates cerebellar development requires identification of TH-regulated gene targets and the cells expressing these genes. Additionally, the process of TH-dependent regulation of gene expression is tightly controlled by mechanisms including regulation of TH transport, TH metabolism, toxicologic inhibition of TH signaling, and control of the nuclear TH response apparatus. This review will describe the functional, cellular, and molecular effects of TH deficit in the developing cerebellum and emphasize the most recent findings regarding TH action in this important brain region.

Iron and Mechanisms of Emotional Behavior

PubMed Central

Kim, Jonghan; Wessling-Resnick, Marianne

2014-01-01

Iron is required for appropriate behavioral organization. Iron deficiency results in poor brain myelination and impaired monoamine metabolism. Glutamate and GABA homeostasis is modified by changes in brain iron status. Such changes not only produce deficits in memory/learning capacity and motor skills, but also emotional and psychological problems. An accumulating body of evidence indicates that both energy metabolism and neurotransmitter homeostasis influence emotional behavior, and both functions are influenced by brain iron status. Like other neurobehavioral aspects, the influence of iron metabolism on mechanisms of emotional behavior are multifactorial: brain region-specific control of behavior, regulation of neurotransmitters and associated proteins, temporal and regional differences in iron requirements, oxidative stress responses to excess iron, sex differences in metabolism, and interactions between iron and other metals. To better understand the role that brain iron plays in emotional behavior and mental health, this review discusses the pathologies associated with anxiety and other emotional disorders with respect to body iron status. PMID:25154570

Academic stress and personality interact to increase the neural response to high-calorie food cues.

PubMed

Neseliler, Selin; Tannenbaum, Beth; Zacchia, Maria; Larcher, Kevin; Coulter, Kirsty; Lamarche, Marie; Marliss, Errol B; Pruessner, Jens; Dagher, Alain

2017-09-01

Psychosocial stress is associated with an increased intake of palatable foods and weight gain in stress-reactive individuals. Personality traits have been shown to predict stress-reactivity. However, it is not known if personality traits influence brain activity in regions implicated in appetite control during psychosocial stress. The current study assessed whether Gray's Behavioural Inhibition System (BIS) scale, a measure of stress-reactivity, was related to the activity of brain regions implicated in appetite control during a stressful period. Twenty-two undergraduate students participated in a functional magnetic resonance imaging (fMRI) experiment once during a non-exam period and once during final exams in a counter-balanced order. In the scanner, they viewed food and scenery pictures. In the exam compared with the non-exam condition, BIS scores related to increased perceived stress and correlated with increased blood-oxygen-level dependent (BOLD) response to high-calorie food images in regions implicated in food reward and subjective value, such as the ventromedial prefrontal cortex, (vmPFC) and the amygdala. BIS scores negatively related to the functional connectivity between the vmPFC and the dorsolateral prefrontal cortex. The results demonstrate that the BIS trait influences stress reactivity. This is observed both as an increased activity in brain regions implicated in computing the value of food cues and decreased connectivity of these regions to prefrontal regions implicated in self-control. This suggests that the effects of real life stress on appetitive brain function and self-control is modulated by a personality trait. This may help to explain why stressful periods can lead to overeating in vulnerable individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Locations and properties of angiotensin II-responsive neurones in the circumventricular region of the duck brain.

PubMed Central

Matsumura, K; Simon, E

1990-01-01

1. In brain slice preparations from the hypothalamus of domestic ducks, single-unit activity was recorded extracellularly to investigate location and properties of angiotensin II (AngII)-responsive neurones in various periventricular regions. 2. When exposing the slice to 10(-7) M-AngII in the perfusion medium, more than 65% of the neurones recorded in the subfornical organ (SFO) were activated (49 out of 75) and none inhibited. In the magnocellular (MC) region of the paraventricular nucleus (PVN) only four out of eighty-one neurones were influenced by AngII; one was inhibited and three were activated. In the anterior third ventricle region (A3V) two out of twenty-one neurones were activated by AngII. In the dorsal periventricular (PeV) region, one out of thirty-seven neurones was activated and one inhibited. The changes in firing rate of AngII-responsive neurones at comparable doses of AngII were generally large in the SFO and A3V but were small in neurones from the MC and PeV regions. 3. Analysis of AngII-responsive SFO neurones consistently revealed a dose-dependent stimulation with a threshold at 10(-9) M-AngII. The AngII antagonist 1Sar-8Ile-AngII (4 x 10(-7) to 10(-6) M) caused reversible, complete or partial suppression of responsiveness to 10(-7) M-AngII. Synaptic blockade with a medium low in Ca2+ and high in Mg2+ did not abolish AngII responsiveness in eight out of ten SFO neurones tested. 4. Angiotensin III affected neither AngII-responsive nor AngII-insensitive neurones. When eighteen AngII-responsive neurones were exposed to hypertonic stimulation (+20 to +30 mosmol/kg) by adding NaCl to the perfusion medium, only one neurone was stimulated and two were inhibited. 5. The results indicate that: (a) the SFO is a specific target for circulating AngII; (b) although neurones in the A3V responsive to AngII are rare, the pronounced excitation of those which were found suggest that neurones in this region might serve as targets for AngII acting from the brain side; (c) neurones in the MC region do not seem to function as direct AngII targets; (d) neuronal AngII responsiveness in the duck's hypothalamus seems to be specific inasmuch as activation by AngII (i) is readily blocked by an AngII antagonist, (ii) cannot be induced by AngIII, and (iii) is not associated, as a rule, with responsiveness to hypertonic stimulation. PMID:2277348

Regional cholinesterase activity in white-throated sparrow brain is differentially affected by acephate (Orthene®)

USGS Publications Warehouse

Vyas, N.B.; Kuenzel, W.J.; Hill, E.F.; Romo, G.A.; Komaragiri, M.V.S.

1996-01-01

Effects of a 14-day dietary exposure to an organophosphorus pesticide, acephate (acetylphosphoramidothioic acid O,S-dimethyl ester), were determined on cholinesterase activity in three regions (basal ganglia, hippocampus, and hypothalamus) of the white-throated sparrow, Zonotrichia albicollis, brain. All three regions experienced depressed cholinesterase activity between 0.5–2 ppm acephate. The regions exhibited cholinesterase recovery at 2–16 ppm acephate; however, cholinesterase activity dropped and showed no recovery at higher dietary levels (>16 ppm acephate). Evidence indicates that the recovery is initiated by the magnitude of depression, not the duration. In general, as acephate concentration increased, differences in ChE activity among brain regions decreased. Three terms are introduced to describe ChE response to acephate exposure: 1) ChE resistance threshold, 2) ChE compensation threshold, and 3) ChE depression threshold. It is hypothesized that adverse effects to birds in the field may occur at pesticide exposure levels customarily considered negligible.

Event-related potentials in response to emotional words in patients with major depressive disorder and healthy controls.

PubMed

Liu, Hong; Yin, Hui-fang; Wu, Da-xing; Xu, Shu-jing

2014-01-01

Dysfunctional cognitive processing and abnormal brain activation in response to emotional stimuli have long been recognized as core features of the major depressive disorder (MDD). The aim of this study was to examine how Chinese patients with MDD process Chinese emotional words presented to either the left (LH) or right hemisphere (RH). Reaction time (RT) and the late positive component of the event-related potential were measured while subjects judged the valence (positive or negative) of emotional words written in Chinese. Compared to healthy controls, patients with MDD exhibited slower RTs in response to negative words. In all subjects, the RTs in response to negative words were significantly faster than RTs in response to positive words presented to the LH, as well as significantly faster than responses to negative words presented to the RH. Compared to healthy controls, MDD patients exhibited reduced activation of the central and left regions of the brain in response to both negative and positive words. In healthy controls, the posterior brain areas were more active than the anterior brain areas when responding to negative words. All individuals showed faster RTs in response to negative words compared to positive words. In addition, MDD patients showed lateralization of brain activity in response to emotional words, whereas healthy individuals did not show this lateralization. Posterior brain areas appear to play an especially important role in discriminating and experiencing negative emotional words. This study provides further evidence in support of the negative bias hypothesis and the emotional processing theory.

A Pilot Study of the Effects of Mindfulness-Based Stress Reduction on Post-traumatic Stress Disorder Symptoms and Brain Response to Traumatic Reminders of Combat in Operation Enduring Freedom/Operation Iraqi Freedom Combat Veterans with Post-traumatic Stress Disorder.

PubMed

Bremner, James Douglas; Mishra, Sanskriti; Campanella, Carolina; Shah, Majid; Kasher, Nicole; Evans, Sarah; Fani, Negar; Shah, Amit Jasvant; Reiff, Collin; Davis, Lori L; Vaccarino, Viola; Carmody, James

2017-01-01

Brain imaging studies in patients with post-traumatic stress disorder (PTSD) have implicated a circuitry of brain regions including the medial prefrontal cortex, amygdala, hippocampus, parietal cortex, and insula. Pharmacological treatment studies have shown a reversal of medial prefrontal deficits in response to traumatic reminders. Mindfulness-based stress reduction (MBSR) is a promising non-pharmacologic approach to the treatment of anxiety and pain disorders. The purpose of this study was to assess the effects of MBSR on PTSD symptoms and brain response to traumatic reminders measured with positron-emission tomography (PET) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) combat veterans with PTSD. We hypothesized that MBSR would show increased prefrontal response to stress and improved PTSD symptoms in veterans with PTSD. Twenty-six OEF/OIF combat veterans with PTSD who had recently returned from a combat zone were block randomized to receive eight sessions of MBSR or present-centered group therapy (PCGT). PTSD patients underwent assessment of PTSD symptoms with the Clinician-Administered PTSD Scale (CAPS), mindfulness with the Five Factor Mindfulness Questionnaire (FFMQ) and brain imaging using PET in conjunction with exposure to neutral and Iraq combat-related slides and sound before and after treatment. Nine patients in the MBSR group and 8 in the PCGT group completed all study procedures. Post-traumatic stress disorder patients treated with MBSR (but not PCGT) had an improvement in PTSD symptoms measured with the CAPS that persisted for 6 months after treatment. MBSR also resulted in an increase in mindfulness measured with the FFMQ. MBSR-treated patients had increased anterior cingulate and inferior parietal lobule and decreased insula and precuneus function in response to traumatic reminders compared to the PCGT group. This study shows that MBSR is a safe and effective treatment for PTSD. Furthermore, MBSR treatment is associated with changes in brain regions that have been implicated in PTSD and are involved in extinction of fear responses to traumatic memories as well as regulation of the stress response.

fMRI study of neural sensitization to hedonic stimuli in long‐term, daily cannabis users

PubMed Central

Dunlop, Joseph; Ketcherside, Ariel; Baine, Jessica; Rhinehardt, Tyler; Kuhn, Brittany; DeWitt, Sam; Alvi, Talha

2016-01-01

Abstract Although there is emergent evidence illustrating neural sensitivity to cannabis cues in cannabis users, the specificity of this effect to cannabis cues as opposed to a generalized hyper‐sensitivity to hedonic stimuli has not yet been directly tested. Using fMRI, we presented 53 daily, long‐term cannabis users and 68 non‐using controls visual and tactile cues for cannabis, a natural reward, and, a sensory‐perceptual control object to evaluate brain response to hedonic stimuli in cannabis users. The results showed an interaction between group and reward type such that the users had greater response during cannabis cues relative to natural reward cues (i.e., fruit) in the orbitofrontal cortex, striatum, anterior cingulate gyrus, and ventral tegmental area compared to non‐users (cluster‐threshold z = 2.3, P < 0.05). In the users, there were positive brain‐behavior correlations between neural response to cannabis cues in fronto‐striatal‐temporal regions and subjective craving, marijuana‐related problems, withdrawal symptoms, and levels of THC metabolites (cluster‐threshold z = 2.3, P < 0.05). These findings demonstrate hyper‐responsivity, and, specificity of brain response to cannabis cues in long‐term cannabis users that are above that of response to natural reward cues. These observations are concordant with incentive sensitization models suggesting sensitization of mesocorticolimbic regions and disruption of natural reward processes following drug use. Although the cross‐sectional nature of this study does not provide information on causality, the positive correlations between neural response and indicators of cannabis use (i.e., THC levels) suggest that alterations in the reward system are, in part, related to cannabis use. Hum Brain Mapp 37:3431–3443, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27168331

Clarifying the Ghrelin System's Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand.

PubMed

Edwards, Alexander; Abizaid, Alfonso

2017-04-19

Ghrelin is a hormone predominantly produced in and secreted from the stomach. Ghrelin is involved in many physiological processes including feeding, the stress response, and in modulating learning, memory and motivational processes. Ghrelin does this by binding to its receptor, the growth hormone secretagogue receptor (GHSR), a receptor found in relatively high concentrations in hypothalamic and mesolimbic brain regions. While the feeding and metabolic effects of ghrelin can be explained by the effects of this hormone on regions of the brain that have a more permeable blood brain barrier (BBB), ghrelin produced within the periphery demonstrates a limited ability to reach extrahypothalamic regions where GHSRs are expressed. Therefore, one of the most pressing unanswered questions plaguing ghrelin research is how GHSRs, distributed in brain regions protected by the BBB, are activated despite ghrelin's predominant peripheral production and poor ability to transverse the BBB. This manuscript will describe how peripheral ghrelin activates central GHSRs to encourage feeding, and how central ghrelin synthesis and ghrelin independent activation of GHSRs may also contribute to the modulation of feeding behaviours.

Motivational Impact of Palatable Food Correlates With Functional Brain Responses to Food Images in Adolescents.

PubMed

Jensen, Chad D; Duraccio, Kara M; Carbine, Kaylie A; Barnett, Kimberly A; Kirwan, C Brock

2017-06-01

To examine associations between motivational impact of palatable foods and neural activity in brain regions involved in inhibitory control among adolescents. Thirty-four adolescents aged 14-20 years underwent functional magnetic resonance imaging while viewing images of high- and low-energy foods. Participants completed the Power of Food Scale (PFS). Whole-brain analyses of variance tested for neural activation differences and correlations between brain activation and PFS scores were tested. We found an interaction between food type (high energy vs. low energy) and PFS scores in the right dorsolateral prefrontal cortex and right inferior parietal lobule. We also found that PFS scores correlated negatively with activation to high-energy foods in prefrontal cortical and parietal regions. These findings suggest that individuals with high motivation for high-energy foods also demonstrate lower neural activation in inhibition-related brain regions when viewing images of high-energy foods, indicating that they may have difficulty inhibiting consumption impulses. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Large-scale brain networks in affective and social neuroscience: Towards an integrative functional architecture of the brain

PubMed Central

Barrett, Lisa Feldman; Satpute, Ajay

2013-01-01

Understanding how a human brain creates a human mind ultimately depends on mapping psychological categories and concepts to physical measurements of neural response. Although it has long been assumed that emotional, social, and cognitive phenomena are realized in the operations of separate brain regions or brain networks, we demonstrate that it is possible to understand the body of neuroimaging evidence using a framework that relies on domain general, distributed structure-function mappings. We review current research in affective and social neuroscience and argue that the emerging science of large-scale intrinsic brain networks provides a coherent framework for a domain-general functional architecture of the human brain. PMID:23352202

Mapping a multidimensional emotion in response to television commercials.

PubMed

Morris, Jon D; Klahr, Nelson J; Shen, Feng; Villegas, Jorge; Wright, Paul; He, Guojun; Liu, Yijun

2009-03-01

Unlike previous emotional studies using functional neuroimaging that have focused on either locating discrete emotions in the brain or linking emotional response to an external behavior, this study investigated brain regions in order to validate a three-dimensional construct--namely pleasure, arousal, and dominance (PAD) of emotion induced by marketing communication. Emotional responses to five television commercials were measured with Advertisement Self-Assessment Manikins (AdSAM) for PAD and with functional magnetic resonance imaging (fMRI) to identify corresponding patterns of brain activation. We found significant differences in the AdSAM scores on the pleasure and arousal rating scales among the stimuli. Using the AdSAM response as a model for the fMRI image analysis, we showed bilateral activations in the inferior frontal gyri and middle temporal gyri associated with the difference on the pleasure dimension, and activations in the right superior temporal gyrus and right middle frontal gyrus associated with the difference on the arousal dimension. These findings suggest a dimensional approach of constructing emotional changes in the brain and provide a better understanding of human behavior in response to advertising stimuli.

Functional brain response to food images in successful adolescent weight losers compared with normal-weight and overweight controls.

PubMed

Jensen, Chad D; Kirwan, C Brock

2015-03-01

Research conducted with adults suggests that successful weight losers demonstrate greater activation in brain regions associated with executive control in response to viewing high-energy foods. No previous studies have examined these associations in adolescents. Functional neuroimaging was used to assess brain response to food images among groups of overweight (OW), normal-weight (NW), and successful weight-losing (SWL) adolescents. Eleven SWL, 12 NW, and 11 OW participants underwent functional magnetic resonance imaging while viewing images of high- and low-energy foods. When viewing high-energy food images, SWLs demonstrated greater activation in the dorsolateral prefrontal cortex (DLPFC) compared with OW and NW controls. Compared with NW and SWL groups, OW individuals demonstrated greater activation in the ventral striatum and anterior cingulate in response to food images. Adolescent SWLs demonstrated greater neural activation in the DLPFC compared with OW/NW controls when viewing high-energy food stimuli, which may indicate enhanced executive control. OW individuals' brain responses to food stimuli may indicate greater reward incentive processes than either SWL or NW groups. © 2015 The Obesity Society.

Acupuncture mobilizes the brain's default mode and its anti-correlated network in healthy subjects.

PubMed

Hui, Kathleen K S; Marina, Ovidiu; Claunch, Joshua D; Nixon, Erika E; Fang, Jiliang; Liu, Jing; Li, Ming; Napadow, Vitaly; Vangel, Mark; Makris, Nikos; Chan, Suk-Tak; Kwong, Kenneth K; Rosen, Bruce R

2009-09-01

Previous work has shown that acupuncture stimulation evokes deactivation of a limbic-paralimbic-neocortical network (LPNN) as well as activation of somatosensory brain regions. This study explores the activity and functional connectivity of these regions during acupuncture vs. tactile stimulation and vs. acupuncture associated with inadvertent sharp pain. Acupuncture during 201 scans and tactile stimulation during 74 scans for comparison at acupoints LI4, ST36 and LV3 was monitored with fMRI and psychophysical response in 48 healthy subjects. Clusters of deactivated regions in the medial prefrontal, medial parietal and medial temporal lobes as well as activated regions in the sensorimotor and a few paralimbic structures can be identified during acupuncture by general linear model analysis and seed-based cross correlation analysis. Importantly, these clusters showed virtual identity with the default mode network and the anti-correlated task-positive network in response to stimulation. In addition, the amygdala and hypothalamus, structures not routinely reported in the default mode literature, were frequently involved in acupuncture. When acupuncture induced sharp pain, the deactivation was attenuated or became activated instead. Tactile stimulation induced greater activation of the somatosensory regions but less extensive deactivation of the LPNN. These results indicate that the deactivation of the LPNN during acupuncture cannot be completely explained by the demand of attention that is commonly proposed in the default mode literature. Our results suggest that acupuncture mobilizes the anti-correlated functional networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response.

Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards.

PubMed

Luo, Shan; Monterosso, John R; Sarpelleh, Kayan; Page, Kathleen A

2015-05-19

Prior studies suggest that fructose compared with glucose may be a weaker suppressor of appetite, and neuroimaging research shows that food cues trigger greater brain reward responses in a fasted relative to a fed state. We sought to determine the effects of ingesting fructose versus glucose on brain, hormone, and appetitive responses to food cues and food-approach behavior. Twenty-four healthy volunteers underwent two functional magnetic resonance imaging (fMRI) sessions with ingestion of either fructose or glucose in a double-blinded, random-order cross-over design. fMRI was performed while participants viewed images of high-calorie foods and nonfood items using a block design. After each block, participants rated hunger and desire for food. Participants also performed a decision task in which they chose between immediate food rewards and delayed monetary bonuses. Hormones were measured at baseline and 30 and 60 min after drink ingestion. Ingestion of fructose relative to glucose resulted in smaller increases in plasma insulin levels and greater brain reactivity to food cues in the visual cortex (in whole-brain analysis) and left orbital frontal cortex (in region-of-interest analysis). Parallel to the neuroimaging findings, fructose versus glucose led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods. These findings suggest that ingestion of fructose relative to glucose results in greater activation of brain regions involved in attention and reward processing and may promote feeding behavior.

Altered brain responses in subjects with irritable bowel syndrome during cued and uncued pain expectation.

PubMed

Hong, J-Y; Naliboff, B; Labus, J S; Gupta, A; Kilpatrick, L A; Ashe-McNalley, C; Stains, J; Heendeniya, N; Smith, S R; Tillisch, K; Mayer, E A

2016-01-01

A majority of the subjects with irritable bowel syndrome (IBS) show increased behavioral and brain responses to expected and delivered aversive visceral stimuli during controlled rectal balloon distension, and during palpation of the sigmoid colon. We aimed to determine if altered brain responses to cued and uncued pain expectation are also seen in the context of a noxious somatic pain stimulus applied to the same dermatome as the sigmoid colon. A task-dependent functional magnetic resonance imaging technique was used to investigate the brain activity of 37 healthy controls (18 females) and 37 IBS subjects (21 females) during: (i) a cued expectation of an electric shock to the abdomen vs a cued safe condition; and (ii) an uncued cross-hair condition in which the threat is primarily based on context vs a cued safe condition. Regions within the salience, attention, default mode, and emotional arousal networks were more activated by the cued abdominal threat condition and the uncued condition than in the cued safe condition. During the uncued condition contrasted to the cued safe condition, IBS subjects (compared to healthy control subjects) showed greater brain activations in the affective (amygdala, anterior insula) and attentional (middle frontal gyrus) regions, and in the thalamus and precuneus. These disease-related differences were primarily seen in female subjects. The observed greater engagement of cognitive and emotional brain networks in IBS subjects during contextual threat may reflect the propensity of IBS subjects to overestimate the likelihood and severity of future abdominal pain. © 2015 John Wiley & Sons Ltd.

Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards

PubMed Central

Luo, Shan; Monterosso, John R.; Sarpelleh, Kayan; Page, Kathleen A.

2015-01-01

Prior studies suggest that fructose compared with glucose may be a weaker suppressor of appetite, and neuroimaging research shows that food cues trigger greater brain reward responses in a fasted relative to a fed state. We sought to determine the effects of ingesting fructose versus glucose on brain, hormone, and appetitive responses to food cues and food-approach behavior. Twenty-four healthy volunteers underwent two functional magnetic resonance imaging (fMRI) sessions with ingestion of either fructose or glucose in a double-blinded, random-order cross-over design. fMRI was performed while participants viewed images of high-calorie foods and nonfood items using a block design. After each block, participants rated hunger and desire for food. Participants also performed a decision task in which they chose between immediate food rewards and delayed monetary bonuses. Hormones were measured at baseline and 30 and 60 min after drink ingestion. Ingestion of fructose relative to glucose resulted in smaller increases in plasma insulin levels and greater brain reactivity to food cues in the visual cortex (in whole-brain analysis) and left orbital frontal cortex (in region-of-interest analysis). Parallel to the neuroimaging findings, fructose versus glucose led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods. These findings suggest that ingestion of fructose relative to glucose results in greater activation of brain regions involved in attention and reward processing and may promote feeding behavior. PMID:25941364

Winning and losing: differences in reward and punishment sensitivity between smokers and nonsmokers.

PubMed

Martin, Laura E; Cox, Lisa S; Brooks, William M; Savage, Cary R

2014-01-01

Smokers show increased brain activation in reward processing regions in response to smoking-related cues, yet few studies have examined secondary rewards not associated with smoking (i.e., money). Inconsistencies exist in the studies that do examine secondary rewards with some studies showing increased brain activation in reward processing brain regions, while others show decreased activation or no difference in activation between smokers and nonsmokers. The goal of the current study is to see if smokers process the evaluation and delivery of equally salient real world rewards similarly or differently than nonsmokers. The current study employed functional magnetic resonance imaging (fMRI) to examine brain responses in smokers and nonsmokers during the evaluation and delivery of monetary gains and losses. In comparison to nonsmokers, smokers showed increased activation in the ventromedial prefrontal cortex to the evaluation of anticipated monetary losses and the brain response. Moreover, smokers compared to nonsmokers showed decreased activation in the inferior frontal gyrus to the delivery of expected monetary gains. Brain activations to both the evaluation of anticipated monetary losses and the delivery of expected monetary gains correlated with increased self-reported smoking craving to relieve negative withdrawal symptoms and craving related to positive aspects of smoking, respectively. Together these results indicate that smokers are hyperresponsive to the evaluation of anticipated punishment and hyporesponsive to the delivery of expected rewards. Although further research is needed, this hypersensitivity to punishments coupled with increased craving may negatively impact quit attempts as smokers anticipate the negative withdrawal symptoms associated with quitting.

The polygenic risk for bipolar disorder influences brain regional function relating to visual and default state processing of emotional information.

PubMed

Dima, Danai; de Jong, Simone; Breen, Gerome; Frangou, Sophia

2016-01-01

Genome-wise association studies have identified a number of common single-nucleotide polymorphisms (SNPs), each of small effect, associated with risk to bipolar disorder (BD). Several risk-conferring SNPs have been individually shown to influence regional brain activation thus linking genetic risk for BD to altered brain function. The current study examined whether the polygenic risk score method, which models the cumulative load of all known risk-conferring SNPs, may be useful in the identification of brain regions whose function may be related to the polygenic architecture of BD. We calculated the individual polygenic risk score for BD (PGR-BD) in forty-one patients with the disorder, twenty-five unaffected first-degree relatives and forty-six unrelated healthy controls using the most recent Psychiatric Genomics Consortium data. Functional magnetic resonance imaging was used to define task-related brain activation patterns in response to facial affect and working memory processing. We found significant effects of the PGR-BD score on task-related activation irrespective of diagnostic group. There was a negative association between the PGR-BD score and activation in the visual association cortex during facial affect processing. In contrast, the PGR-BD score was associated with failure to deactivate the ventromedial prefrontal region of the default mode network during working memory processing. These results are consistent with the threshold-liability model of BD, and demonstrate the usefulness of the PGR-BD score in identifying brain functional alternations associated with vulnerability to BD. Additionally, our findings suggest that the polygenic architecture of BD is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions.

Increased power spectral density in resting-state pain-related brain networks in fibromyalgia.

PubMed

Kim, Ji-Young; Kim, Seong-Ho; Seo, Jeehye; Kim, Sang-Hyon; Han, Seung Woo; Nam, Eon Jeong; Kim, Seong-Kyu; Lee, Hui Joong; Lee, Seung-Jae; Kim, Yang-Tae; Chang, Yongmin

2013-09-01

Fibromyalgia (FM), characterized by chronic widespread pain, is known to be associated with heightened responses to painful stimuli and atypical resting-state functional connectivity among pain-related regions of the brain. Previous studies of FM using resting-state functional magnetic resonance imaging (rs-fMRI) have focused on intrinsic functional connectivity, which maps the spatial distribution of temporal correlations among spontaneous low-frequency fluctuation in functional MRI (fMRI) resting-state data. In the current study, using rs-fMRI data in the frequency domain, we investigated the possible alteration of power spectral density (PSD) of low-frequency fluctuation in brain regions associated with central pain processing in patients with FM. rsfMRI data were obtained from 19 patients with FM and 20 age-matched healthy female control subjects. For each subject, the PSDs for each brain region identified from functional connectivity maps were computed for the frequency band of 0.01 to 0.25 Hz. For each group, the average PSD was determined for each brain region and a 2-sample t test was performed to determine the difference in power between the 2 groups. According to the results, patients with FM exhibited significantly increased frequency power in the primary somatosensory cortex (S1), supplementary motor area (SMA), dorsolateral prefrontal cortex, and amygdala. In patients with FM, the increase in PSD did not show an association with depression or anxiety. Therefore, our findings of atypical increased frequency power during the resting state in pain-related brain regions may implicate the enhanced resting-state baseline neural activity in several brain regions associated with pain processing in FM. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

How Hot Are They? Neural Correlates of Genital Arousal: An Infrared Thermographic and Functional Magnetic Resonance Imaging Study of Sexual Arousal in Men and Women.

PubMed

Parada, Mayte; Gérard, Marina; Larcher, Kevin; Dagher, Alain; Binik, Yitzchak M

2018-02-01

The few studies that have examined the neural correlates of genital arousal have focused on men and are methodologically hard to compare. To investigate the neural correlates of peripheral physiologic sexual arousal using identical methodology for men and women. 2 groups (20 men, 20 women) viewed movie clips (erotic, humor) while genital temperature was continuously measured using infrared thermal imaging. Participants also continuously evaluated changes in their subjective arousal and answered discrete questions about liking the movies and wanting sexual stimulation. Brain activity, indicated by blood oxygen level-dependent (BOLD) response, was measured using functional magnetic resonance imaging. BOLD responses, genital temperature, and subjective sexual arousal. BOLD activity in a number of brain regions was correlated with changes in genital temperature in men and women; however, activation in women appeared to be more extensive than in men, including the anterior and posterior cingulate cortex, right cerebellum, insula, frontal operculum, and paracingulate gyrus. Examination of the strength of the correlation between BOLD response and genital temperature showed that women had a stronger brain-genital relation compared with men in a number of regions. There were no brain regions in men with stronger brain-genital correlations than in women. Our findings shed light on the neurophysiologic processes involved in genital arousal for men and women. Further research examining the specific brain regions that mediate our findings is necessary to pave the way for clinical application. A strength of the study is the use of thermography, which allows for a direct comparison of the neural correlates of genital arousal in men and women. This study has the common limitations of most laboratory-based sexual arousal research, including sampling bias, lack of ecologic validity, and equipment limitations, and those common to neuroimaging research, including BOLD signal interpretation and neuroimaging analysis issues. Our findings provide direct sex comparisons of the neural correlates of genital arousal in men and women and suggest that brain-genital correlations could be stronger in women. Parada M, Gérard M, Larcher K, et al. How Hot Are They? Neural Correlates of Genital Arousal: An Infrared Thermographic and Functional Magnetic Resonance Imaging Study of Sexual Arousal in Men and Women. J Sex Med 2018;15:217-229. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Posttraumatic Stress Disorder: A Theoretical Model of the Hyperarousal Subtype

PubMed Central

Weston, Charles Stewart E.

2014-01-01

Posttraumatic stress disorder (PTSD) is a frequent and distressing mental disorder, about which much remains to be learned. It is a heterogeneous disorder; the hyperarousal subtype (about 70% of occurrences and simply termed PTSD in this paper) is the topic of this article, but the dissociative subtype (about 30% of occurrences and likely involving quite different brain mechanisms) is outside its scope. A theoretical model is presented that integrates neuroscience data on diverse brain regions known to be involved in PTSD, and extensive psychiatric findings on the disorder. Specifically, the amygdala is a multifunctional brain region that is crucial to PTSD, and processes peritraumatic hyperarousal on grounded cognition principles to produce hyperarousal symptoms. Amygdala activity also modulates hippocampal function, which is supported by a large body of evidence, and likewise amygdala activity modulates several brainstem regions, visual cortex, rostral anterior cingulate cortex (rACC), and medial orbitofrontal cortex (mOFC), to produce diverse startle, visual, memory, numbing, anger, and recklessness symptoms. Additional brain regions process other aspects of peritraumatic responses to produce further symptoms. These contentions are supported by neuroimaging, neuropsychological, neuroanatomical, physiological, cognitive, and behavioral evidence. Collectively, the model offers an account of how responses at the time of trauma are transformed into an extensive array of the 20 PTSD symptoms that are specified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition. It elucidates the neural mechanisms of a specific form of psychopathology, and accords with the Research Domain Criteria framework. PMID:24772094

Methamphetamine-induced neuronal necrosis: the role of electrographic seizure discharges

PubMed Central

Fujikawa, Denson G.; Pais, Emil S.; Aviles, Ernesto R.; Hsieh, Kung-Chiao; Bashir, Muhammad Tariq

2016-01-01

We have evidence that methamphetamine (METH)-induced neuronal death is morphologically necrotic, not apoptotic, as is currently believed, and that electrographic seizures may be responsible. We administered 40 mg/kg i.p. to 12 male C57BL/6 mice and monitored EEGs continuously and rectal temperatures every 15 min, keeping rectal temperatures <41.0 °C. Seven of the 12 mice had repetitive electrographic seizure discharges (RESDs) and 5 did not. The RESDs were often not accompanied by behavioral signs of seizures–i.e., they were often not accompanied by clonic forelimb movements. The 7 mice with RESDs had acidophilic neurons (the H&E light-microscopic equivalent of necrotic neurons by ultrastructural examination) in all of 7 brain regions (hippocampal CA1, CA2, CA3 and hilus, amygdala, piriform cortex and entorhinal cortex), the same brain regions damaged following generalized seizures, 24 h after METH administration. The 5 mice without RESDs had a few acidophilic neurons in 4 of the 7 brain regions, but those with RESDs had significantly more in 6 of the 7 brain regions. Maximum rectal temperatures were comparable in mice with and without RESDs, so that cannot explain the difference between the two groups with respect to METH-induced neuronal death. Our data show that METH-induced neuronal death is morphologically necrotic, that EEGs must be recorded to detect electrographic seizure activity in rodents without behavioral evidence of seizures, and that RESDs may be responsible for METH-induced neuronal death. PMID:26562800

Use of Multichannel Near Infrared Spectroscopy to Study Relationships Between Brain Regions and Neurocognitive Tasks of Selective/Divided Attention and 2-Back Working Memory.

PubMed

Tomita, Nozomi; Imai, Shoji; Kanayama, Yusuke; Kawashima, Issaku; Kumano, Hiroaki

2017-06-01

While dichotic listening (DL) was originally intended to measure bottom-up selective attention, it has also become a tool for measuring top-down selective attention. This study investigated the brain regions related to top-down selective and divided attention DL tasks and a 2-back task using alphanumeric and Japanese numeric sounds. Thirty-six healthy participants underwent near-infrared spectroscopy scanning while performing a top-down selective attentional DL task, a top-down divided attentional DL task, and a 2-back task. Pearson's correlations were calculated to show relationships between oxy-Hb concentration in each brain region and the score of each cognitive task. Different brain regions were activated during the DL and 2-back tasks. Brain regions activated in the top-down selective attention DL task were the left inferior prefrontal gyrus and left pars opercularis. The left temporopolar area was activated in the top-down divided attention DL task, and the left frontopolar area and left dorsolateral prefrontal cortex were activated in the 2-back task. As further evidence for the finding that each task measured different cognitive and brain area functions, neither the percentages of correct answers for the three tasks nor the response times for the selective attentional task and the divided attentional task were correlated to one another. Thus, the DL and 2-back tasks used in this study can assess multiple areas of cognitive, brain-related dysfunction to explore their relationship to different psychiatric and neurodevelopmental disorders.

Defining functional SMA and pre-SMA subregions in human MFC using resting state fMRI: functional connectivity-based parcellation method.

PubMed

Kim, Jae-Hun; Lee, Jong-Min; Jo, Hang Joon; Kim, Sook Hui; Lee, Jung Hee; Kim, Sung Tae; Seo, Sang Won; Cox, Robert W; Na, Duk L; Kim, Sun I; Saad, Ziad S

2010-02-01

Noninvasive parcellation of the human cerebral cortex is an important goal for understanding and examining brain functions. Recently, the patterns of anatomical connections using diffusion tensor imaging (DTI) have been used to parcellate brain regions. Here, we present a noninvasive parcellation approach that uses "functional fingerprints" obtained by correlation measures on resting state functional magnetic resonance imaging (fMRI) data to parcellate brain regions. In other terms, brain regions are parcellated based on the similarity of their connection--as reflected by correlation during resting state--to the whole brain. The proposed method was used to parcellate the medial frontal cortex (MFC) into supplementary motor areas (SMA) and pre-SMA subregions. In agreement with anatomical landmark-based parcellation, we find that functional fingerprint clustering of the MFC results in anterior and posterior clusters. The probabilistic maps from 12 subjects showed that the anterior cluster is mainly located rostral to the vertical commissure anterior (VCA) line, whereas the posterior cluster is mainly located caudal to VCA line, suggesting the homologues of pre-SMA and SMA. The functional connections from the putative pre-SMA cluster were connected to brain regions which are responsible for complex/cognitive motor control, whereas those from the putative SMA cluster were connected to brain regions which are related to the simple motor control. These findings demonstrate the feasibility of the functional connectivity-based parcellation of the human cerebral cortex using resting state fMRI. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Specific regions of the brain are capable of fructose metabolism.

PubMed

Oppelt, Sarah A; Zhang, Wanming; Tolan, Dean R

2017-02-15

High fructose consumption in the Western diet correlates with disease states such as obesity and metabolic syndrome complications, including type II diabetes, chronic kidney disease, and non-alcoholic fatty acid liver disease. Liver and kidneys are responsible for metabolism of 40-60% of ingested fructose, while the physiological fate of the remaining fructose remains poorly understood. The primary metabolic pathway for fructose includes the fructose-transporting solute-like carrier transport proteins 2a (SLC2a or GLUT), including GLUT5 and GLUT9, ketohexokinase (KHK), and aldolase. Bioinformatic analysis of gene expression encoding these proteins (glut5, glut9, khk, and aldoC, respectively) identifies other organs capable of this fructose metabolism. This analysis predicts brain, lymphoreticular tissue, placenta, and reproductive tissues as possible additional organs for fructose metabolism. While expression of these genes is highest in liver, the brain is predicted to have expression levels of these genes similar to kidney. RNA in situ hybridization of coronal slices of adult mouse brains validate the in silico expression of glut5, glut9, khk, and aldoC, and show expression across many regions of the brain, with the most notable expression in the cerebellum, hippocampus, cortex, and olfactory bulb. Dissected samples of these brain regions show KHK and aldolase enzyme activity 5-10 times the concentration of that in liver. Furthermore, rates of fructose oxidation in these brain regions are 15-150 times that of liver slices, confirming the bioinformatics prediction and in situ hybridization data. This suggests that previously unappreciated regions across the brain can use fructose, in addition to glucose, for energy production. Copyright © 2016 Elsevier B.V. All rights reserved.

Specific regions of the brain are capable of fructose metabolism

PubMed Central

Oppelt, Sarah A.; Zhang, Wanming; Tolan, Dean R.

2017-01-01

High fructose consumption in the Western diet correlates with disease states such as obesity and metabolic syndrome complications, including type II diabetes, chronic kidney disease, and nonalcoholic fatty acid liver disease. Liver and kidneys are responsible for metabolism of 40–60% of ingested fructose, while the physiological fate of the remaining fructose remains poorly understood. The primary metabolic pathway for fructose includes the fructose-transporting solute-like carrier transport proteins 2a (SLC2a or GLUT), including GLUT5 and GLUT9, ketohexokinase (KHK), and aldolase. Bioinformatic analysis of gene expression encoding these proteins (glut5, glut9, khk, and aldoC, respectively) identifies other organs capable of this fructose metabolism. This analysis predicts brain, lymphoreticular tissue, placenta, and reproductive tissues as possible additional organs for fructose metabolism. While expression of these genes is highest in liver, the brain is predicted to have expression levels of these genes similar to kidney. RNA in situ hybridization of coronal slices of adult mouse brains validate the in silico expression of glut5, glut9, khk, and aldoC, and show expression across many regions of the brain, with the most notable expression in the cerebellum, hippocampus, cortex, and olfactory bulb. Dissected samples of these brain regions show KHK and aldolase enzyme activity 5–10 times the concentration of that in liver. Furthermore, rates of fructose oxidation in these brain regions are 15–150 times that of liver slices, confirming the bioinformatics prediction and in situ hybridization data. This suggests that previously unappreciated regions across the brain can use fructose, in addition to glucose, for energy production. PMID:28034722

Imaging of Glial Cell Activation and White Matter Integrity in Brains of Active and Recently Retired National Football League Players.

PubMed

Coughlin, Jennifer M; Wang, Yuchuan; Minn, Il; Bienko, Nicholas; Ambinder, Emily B; Xu, Xin; Peters, Matthew E; Dougherty, John W; Vranesic, Melin; Koo, Soo Min; Ahn, Hye-Hyun; Lee, Merton; Cottrell, Chris; Sair, Haris I; Sawa, Akira; Munro, Cynthia A; Nowinski, Christopher J; Dannals, Robert F; Lyketsos, Constantine G; Kassiou, Michael; Smith, Gwenn; Caffo, Brian; Mori, Susumu; Guilarte, Tomas R; Pomper, Martin G

2017-01-01

Microglia, the resident immune cells of the central nervous system, play an important role in the brain's response to injury and neurodegenerative processes. It has been proposed that prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury. To measure translocator protein 18 kDa (TSPO), a marker of activated glial cell response, in a cohort of National Football League (NFL) players and control participants, and to report measures of white matter integrity. This cross-sectional, case-control study included young active (n = 4) or former (n = 10) NFL players recruited from across the United States, and 16 age-, sex-, highest educational level-, and body mass index-matched control participants. This study was conducted at an academic research institution in Baltimore, Maryland, from January 29, 2015, to February 18, 2016. Positron emission tomography-based regional measures of TSPO using [11C]DPA-713, diffusion tensor imaging measures of regional white matter integrity, regional volumes on structural magnetic resonance imaging, and neuropsychological performance. The mean (SD) ages of the 14 NFL participants and 16 control participants were 31.3 (6.1) years and 27.6 (4.9) years, respectively. Players reported a mean (SD) of 7.0 (6.4) years (range, 1-21 years) since the last self-reported concussion. Using [11C]DPA-713 positron emission tomographic data from 12 active or former NFL players and 11 matched control participants, the NFL players showed higher total distribution volume in 8 of the 12 brain regions examined (P < .004). We also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players compared with 15 control participants. In contrast, these young players did not differ from control participants in regional brain volumes or in neuropsychological performance. The results suggest that localized brain injury and repair, indicated by higher TSPO signal and white matter changes, may be associated with NFL play. Further study is needed to confirm these findings and to determine whether TSPO signal and white matter changes in young NFL athletes are related to later onset of neuropsychiatric symptoms.

Face processing in autism spectrum disorders: from brain regions to brain networks

PubMed Central

Nomi, Jason S.; Uddin, Lucina Q.

2015-01-01

Autism spectrum disorder (ASD) is characterized by reduced attention to social stimuli including the human face. This hypo-responsiveness to stimuli that are engaging to typically developing individuals may result from dysfunctioning motivation, reward, and attention systems in the brain. Here we review an emerging neuroimaging literature that emphasizes a shift from focusing on hypo-activation of isolated brain regions such as the fusiform gyrus, amygdala, and superior temporal sulcus in ASD to a more holistic approach to understanding face perception as a process supported by distributed cortical and subcortical brain networks. We summarize evidence for atypical activation patterns within brain networks that may contribute to social deficits characteristic of the disorder. We conclude by pointing to gaps in the literature and future directions that will continue to shed light on aspects of face processing in autism that are still under-examined. In particular, we highlight the need for more developmental studies and studies examining ecologically valid and naturalistic social stimuli. PMID:25829246

The visual cognitive network, but not the visual sensory network, is affected in amnestic mild cognitive impairment: a study of brain oscillatory responses.

PubMed

Yener, Görsev G; Emek-Savaş, Derya Durusu; Güntekin, Bahar; Başar, Erol

2014-10-17

Mild Cognitive Impairment (MCI) is considered in many as prodromal stage of Alzheimer's disease (AD). Event-related oscillations (ERO) reflect cognitive responses of brain whereas sensory-evoked oscillations (SEO) inform about sensory responses. For this study, we compared visual SEO and ERO responses in MCI to explore brain dynamics (BACKGROUND). Forty-three patients with MCI (mean age=74.0 year) and 41 age- and education-matched healthy-elderly controls (HC) (mean age=71.1 year) participated in the study. The maximum peak-to-peak amplitudes for each subject's averaged delta response (0.5-3.0 Hz) were measured from two conditions (simple visual stimulation and classical visual oddball paradigm target stimulation) (METHOD). Overall, amplitudes of target ERO responses were higher than SEO amplitudes. The preferential location for maximum amplitude values was frontal lobe for ERO and occipital lobe for SEO. The ANOVA for delta responses showed significant results for the group Xparadigm. Post-hoc tests indicated that (1) the difference between groups were significant for target delta responses, but not for SEO, (2) ERO elicited higher responses for HC than MCI patients, and (3) females had higher target ERO than males and this difference was pronounced in the control group (RESULTS). Overall, cognitive responses display almost double the amplitudes of sensory responses over frontal regions. The topography of oscillatory responses differs depending on stimuli: visualsensory responses are highest over occipitals and -cognitive responses over frontal regions. A group effect is observed in MCI indicating that visual sensory and cognitive circuits behave differently indicating preserved visual sensory responses, but decreased cognitive responses (CONCLUSION). Copyright © 2014 Elsevier B.V. All rights reserved.

Interleukin-6 -174 and -572 genotypes and the volume of deep gray matter in preterm infants.

PubMed

Reiman, Milla; Parkkola, Riitta; Lapinleimu, Helena; Lehtonen, Liisa; Haataja, Leena

2009-01-01

Preterm infants have smaller cerebral and cerebellar volumes at term compared with term born infants. Perinatal factors leading to the reduction in volumes are not well known. IL-6 -174 and -572 genotypes partly regulate individual immunologic responses and have also been connected with deviant neurologic development in preterm infants. Our hypothesis was that IL-6 -174 and -572 genetic polymorphisms are associated with brain lesions and regional brain volumes in very low birth weight or in very preterm infants. DNA was genotyped for IL-6 -174 and -572 polymorphisms (GG/GC/CC). Study infants (n = 175) were categorized into three groups according to the most pathologic brain finding in ultrasound examinations until term. The brain MRI performed at term was analyzed for regional brain volumes. Analyzed IL-6 genotypes did not show statistically significant association with structural brain lesions. However, IL-6 -174 CC and -572 GG genotypes associated with reduced volume of one brain region, the combined volume of basal ganglia and thalami, both in univariate and in multivariate analyses (p = 0.009, 0.009, respectively). The association of IL-6 -174 and -572 genetic polymorphisms with smaller volumes in deep gray matter provides us new ways to understand the processes leading to neurologic impairments in preterm infants.

Opiates and cerebral functional activity in rats

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

Trusk, T.C.

1986-01-01

Cerebral activity was measured using the free-fatty acid (1-/sup 14/C) octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional responsemore » to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions.« less

Variations of response time in a selective attention task are linked to variations of functional connectivity in the attentional network.

PubMed

Prado, Jérôme; Carp, Joshua; Weissman, Daniel H

2011-01-01

Although variations of response time (RT) within a particular experimental condition are typically ignored, they may sometimes reflect meaningful changes in the efficiency of cognitive and neural processes. In the present study, we investigated whether trial-by-trial variations of response time (RT) in a cross-modal selective attention task were associated with variations of functional connectivity between brain regions that are thought to underlie attention. Sixteen healthy young adults performed an audiovisual selective attention task, which involved attending to a relevant visual letter while ignoring an irrelevant auditory letter, as we recorded their brain activity using functional magnetic resonance imaging (fMRI). In line with predictions, variations of RT were associated with variations of functional connectivity between the anterior cingulate cortex and various other brain regions that are posited to underlie attentional control, such as the right dorsolateral prefrontal cortex and bilateral regions of the posterior parietal cortex. They were also linked to variations of functional connectivity between anatomically early and anatomically late regions of the relevant-modality visual cortex whose communication is thought to be modulated by attentional control processes. By revealing that variations of RT in a selective attention task are linked to variations of functional connectivity in the attentional network, the present findings suggest that variations of attention may contribute to trial-by-trial fluctuations of behavioral performance. Copyright © 2010 Elsevier Inc. All rights reserved.

Epidemic spreading model to characterize misfolded proteins propagation in aging and associated neurodegenerative disorders.

PubMed

Iturria-Medina, Yasser; Sotero, Roberto C; Toussaint, Paule J; Evans, Alan C

2014-11-01

Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders.

Acupuncture Modulates Resting State Connectivity in Default and Sensorimotor Brain Networks

PubMed Central

Dhond, Rupali P.; Yeh, Calvin; Park, Kyungmo; Kettner, Norman; Napadow, Vitaly

2008-01-01

Previous studies have defined low-frequency, spatially consistent networks in resting fMRI data which may reflect functional connectivity. We sought to explore how a complex somatosensory stimulation, acupuncture, influences intrinsic connectivity in two of these networks: the default mode network (DMN) and sensorimotor network (SMN). We analyzed resting fMRI data taken before and after verum and sham acupuncture. Electrocardiography data was used to infer autonomic modulation through measures of heart rate variability (HRV). Probabilistic independent component analysis was used to separate resting fMRI data into DMN and SMN components. Following verum, but not sham, acupuncture there was increased DMN connectivity with pain (anterior cingulate cortex (ACC), periaqueductal gray), affective (amygdala, ACC), and memory (hippocampal formation, middle temporal gyrus) related brain regions. Furthermore, increased DMN connectivity with the hippocampal formation, a region known to support memory and interconnected with autonomic brain regions, was negatively correlated with acupuncture-induced increase in a sympathetic related HRV metric (LFu), and positively correlated with a parasympathetic related metric (HFu). Following verum, but not sham, acupuncture there was also increased SMN connectivity with pain related brain regions (ACC, cerebellum). We attribute differences between verum and sham acupuncture to more varied and stronger sensations evoked by verum acupuncture. Our results demonstrate for the first time that acupuncture can enhance the post-stimulation spatial extent of resting brain networks to include anti-nociceptive, memory, and affective brain regions. This modulation and sympathovagal response may relate to acupuncture analgesia and other potential therapeutic effects. PMID:18337009

Epidemic Spreading Model to Characterize Misfolded Proteins Propagation in Aging and Associated Neurodegenerative Disorders

PubMed Central

Iturria-Medina, Yasser; Sotero, Roberto C.; Toussaint, Paule J.; Evans, Alan C.

2014-01-01

Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders. PMID:25412207

Antioxidant mediated response of Scoparia dulcis in noise-induced redox imbalance and immunohistochemical changes in rat brain.

PubMed

Wankhar, Wankupar; Srinivasan, Sakthivel; Rajan, Ravindran; Sheeladevi, Rathinasamy

2017-01-19

Noise has been regarded as an environmental/occupational stressor that causes damages to both auditory and non-auditory organs. Prolonged exposure to these mediators of stress has often resulted in detrimental effect, where oxidative/nitrosative stress plays a major role. Hence, it would be appropriate to examine the possible role of free radicals in brain discrete regions and the "antioxidants" mediated response of S. dulcis. Animals were subjected to noise stress for 15 days (100 dB/4 hours/day) and estimation of endogenous free radical and antioxidant activity were carried out on brain discrete regions (the cerebral cortex, cerebellum, brainstem, striatum, hippocampus and hypothalamus). The result showed that exposure to noise could alleviate endogenous free radical generation and altered antioxidant status in brain discrete regions when compared to that of the control groups. This alleviated free radical generation (H 2 O 2 and NO) is well supported by an upregulated protein expression on immunohistochemistry of both iNOS and nNOS in the cerebral cortex on exposure to noise stress. These findings suggest that increased free radical generation and altered anti-oxidative status can cause redox imbalance in the brain discrete regions. However, free radical scavenging activity of the plant was evident as the noise exposed group treated with S. dulcis[200 mg/(kg·b·w)] displayed a therapeutic effect by decreasing the free radical level and regulate the anti-oxidative status to that of control animals. Hence, it can be concluded that the efficacy of S. dulcis could be attributed to its free radical scavenging activity and anti-oxidative property.

Antioxidant mediated response of Scoparia dulcis in noise-induced redox imbalance and immunohistochemical changes in rat brain

PubMed Central

Wankhar, Wankupar; Srinivasan, Sakthivel; Rajan, Ravindran; Sheeladevi, Rathinasamy

2017-01-01

Noise has been regarded as an environmental/occupational stressor that causes damages to both auditory and non-auditory organs. Prolonged exposure to these mediators of stress has often resulted in detrimental effect, where oxidative/nitrosative stress plays a major role. Hence, it would be appropriate to examine the possible role of free radicals in brain discrete regions and the "antioxidants" mediated response of S. dulcis. Animals were subjected to noise stress for 15 days (100 dB/4 hours/day) and estimation of endogenous free radical and antioxidant activity were carried out on brain discrete regions (the cerebral cortex, cerebellum, brainstem, striatum, hippocampus and hypothalamus). The result showed that exposure to noise could alleviate endogenous free radical generation and altered antioxidant status in brain discrete regions when compared to that of the control groups. This alleviated free radical generation (H2O2 and NO) is well supported by an upregulated protein expression on immunohistochemistry of both iNOS and nNOS in the cerebral cortex on exposure to noise stress. These findings suggest that increased free radical generation and altered anti-oxidative status can cause redox imbalance in the brain discrete regions. However, free radical scavenging activity of the plant was evident as the noise exposed group treated with S. dulcis[200 mg/(kg·b·w)] displayed a therapeutic effect by decreasing the free radical level and regulate the anti-oxidative status to that of control animals. Hence, it can be concluded that the efficacy of S. dulcis could be attributed to its free radical scavenging activity and anti-oxidative property. PMID:28808196

Task difficulty modulates brain-behavior correlations in language production and cognitive control: Behavioral and fMRI evidence from a phonological go/no-go picture-naming paradigm.

PubMed

Zhang, Haoyun; Eppes, Anna; Beatty-Martínez, Anne; Navarro-Torres, Christian; Diaz, Michele T

2018-06-19

Language production and cognitive control are complex processes that involve distinct yet interacting brain networks. However, the extent to which these processes interact and their neural bases have not been thoroughly examined. Here, we investigated the neural and behavioral bases of language production and cognitive control via a phonological go/no-go picture-naming task. Naming difficulty and cognitive control demands (i.e., conflict monitoring and response inhibition) were manipulated by varying the proportion of naming trials (go trials) and inhibition trials (no-go trials) across task runs. The results demonstrated that as task demands increased, participants' behavioral performance declined (i.e., longer reaction times on naming trials, more commission errors on inhibition trials) whereas brain activation generally increased. Increased activation was found not only within the language network but also in domain-general control regions. Additionally, right superior and inferior frontal and left supramarginal gyri were sensitive to increased task difficulty during both language production and response inhibition. We also found both positive and negative brain-behavior correlations. Most notably, increased activation in sensorimotor regions, such as precentral and postcentral gyri, was associated with better behavioral performance, in both successful picture naming and successful inhibition. Moreover, comparing the strength of correlations across conditions indicated that the brain-behavior correlations in sensorimotor regions that were associated with improved performance became stronger as task demands increased. Overall, our results suggest that cognitive control demands affect language production, and that successfully coping with increases in task difficulty relies on both language-specific and domain-general cognitive control regions.

Estimating direction in brain-behavior interactions: Proactive and reactive brain states in driving.

PubMed

Garcia, Javier O; Brooks, Justin; Kerick, Scott; Johnson, Tony; Mullen, Tim R; Vettel, Jean M

2017-04-15

Conventional neuroimaging analyses have ascribed function to particular brain regions, exploiting the power of the subtraction technique in fMRI and event-related potential analyses in EEG. Moving beyond this convention, many researchers have begun exploring network-based neurodynamics and coordination between brain regions as a function of behavioral parameters or environmental statistics; however, most approaches average evoked activity across the experimental session to study task-dependent networks. Here, we examined on-going oscillatory activity as measured with EEG and use a methodology to estimate directionality in brain-behavior interactions. After source reconstruction, activity within specific frequency bands (delta: 2-3Hz; theta: 4-7Hz; alpha: 8-12Hz; beta: 13-25Hz) in a priori regions of interest was linked to continuous behavioral measurements, and we used a predictive filtering scheme to estimate the asymmetry between brain-to-behavior and behavior-to-brain prediction using a variant of Granger causality. We applied this approach to a simulated driving task and examined directed relationships between brain activity and continuous driving performance (steering behavior or vehicle heading error). Our results indicated that two neuro-behavioral states may be explored with this methodology: a Proactive brain state that actively plans the response to the sensory information and is characterized by delta-beta activity, and a Reactive brain state that processes incoming information and reacts to environmental statistics primarily within the alpha band. Published by Elsevier Inc.

Age differentially influences estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) gene expression in specific regions of the rat brain.

PubMed

Wilson, Melinda E; Rosewell, Katherine L; Kashon, Michael L; Shughrue, Paul J; Merchenthaler, Istvan; Wise, Phyllis M

2002-03-31

Estradiol's ability to influence neurochemical events that are critical to female reproductive cyclicity and behavior decreases with age. We tested the hypothesis that decreases in estrogen receptor-alpha (ERalpha) and/or ERbeta mRNA explain the brain's declining responsiveness to estradiol. We assessed ERalpha and ERbeta mRNA levels in intact and ovariectomized estradiol-treated rats. ERbeta mRNA was detected in several brain regions and decreased by middle-age in the cerebral cortex and supraoptic nucleus of estradiol-treated rats. ERbeta mRNA levels exhibited a diurnal rhythm in the suprachiasmatic nucleus of young and middle-aged rats and this rhythm was blunted in old rats. We examined ERalpha mRNA in the periventricular preoptic, medial preoptic, ventromedial and arcuate nuclei, and it was decreased only in the periventricular preoptic nucleus of the old rats. In summary, the expression of ERalpha and ERbeta mRNAs is differentially modulated in the aging brain and changes are region specific.

Learning Temporal Statistics for Sensory Predictions in Aging.

PubMed

Luft, Caroline Di Bernardi; Baker, Rosalind; Goldstone, Aimee; Zhang, Yang; Kourtzi, Zoe

2016-03-01

Predicting future events based on previous knowledge about the environment is critical for successful everyday interactions. Here, we ask which brain regions support our ability to predict the future based on implicit knowledge about the past in young and older age. Combining behavioral and fMRI measurements, we test whether training on structured temporal sequences improves the ability to predict upcoming sensory events; we then compare brain regions involved in learning predictive structures between young and older adults. Our behavioral results demonstrate that exposure to temporal sequences without feedback facilitates the ability of young and older adults to predict the orientation of an upcoming stimulus. Our fMRI results provide evidence for the involvement of corticostriatal regions in learning predictive structures in both young and older learners. In particular, we showed learning-dependent fMRI responses for structured sequences in frontoparietal regions and the striatum (putamen) for young adults. However, for older adults, learning-dependent activations were observed mainly in subcortical (putamen, thalamus) regions but were weaker in frontoparietal regions. Significant correlations of learning-dependent behavioral and fMRI changes in these regions suggest a strong link between brain activations and behavioral improvement rather than general overactivation. Thus, our findings suggest that predicting future events based on knowledge of temporal statistics engages brain regions involved in implicit learning in both young and older adults.

Personality and emotion: test of Gray's personality theory by means of an fMRI study.

PubMed

Reuter, M; Stark, R; Hennig, J; Walter, B; Kirsch, P; Schienle, A; Vaitl, D

2004-06-01

Although it is known that there are fundamental personality differences in the behavioral responses to emotional stimuli, traits have scarcely been investigated in this context by means of functional imaging studies. To maximize the variance with respect to personality, the authors tested 12 control subjects and 12 subjects who had sadomasochistic experiences with respect to the relationship between J. A. Gray's (1970) personality dimensions, the behavioral approach system (BAS) and the behavioral inhibition system (BIS), and brain activity in regions of interest. The BIS was associated with activity in numerous brain areas in response to fear, disgust, and erotic visual stimuli, whereas few associations could he detected between the BAS and brain activity in response to disgust and erotic stimuli. ((c) 2004 APA, all rights reserved)

Regional Blood-Brain Barrier Responses to Central Cholinergic Activity

DTIC Science & Technology

1989-07-30

i.e., oxotremorine, pilocarpine, carbachol , physostigmine [Olney et al., 1983]). These are some of the same regions affected by soman-induced...Diehl et al., 1984). Carbachol kindling also has been reported (Wasterlain, 1989), linking the cholinergic system to an increase in the sensitivity to

Regional Gray Matter Density Associated with Cognitive Reflectivity–Impulsivity: Evidence from Voxel-Based Morphometry

PubMed Central

Yokoyama, Ryoichi; Nozawa, Takayuki; Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Hanihara, Mayu; Sassa, Yuko; Kawashima, Ryuta

2015-01-01

When faced with a problem or choice, humans can use two different strategies: “cognitive reflectivity,” which involves slow responses and fewer mistakes, or “cognitive impulsivity,” which comprises of quick responses and more mistakes. Different individuals use these two strategies differently. To our knowledge, no study has directly investigated the brain regions involved in reflectivity–impulsivity; therefore, this study focused on associations between these cognitive strategies and the gray matter structure of several brain regions. In order to accomplish this, we enrolled 776 healthy, right-handed individuals (432 men and 344 women; 20.7 ± 1.8 years) and used voxel-based morphometry with administration of a cognitive reflectivity–impulsivity questionnaire. We found that high cognitive reflectivity was associated with greater regional gray matter density in the ventral medial prefrontal cortex. Our finding suggests that this area plays an important role in defining an individual’s trait associated with reflectivity and impulsivity. PMID:25803809

Integration of faces and vocalizations in ventral prefrontal cortex: Implications for the evolution of audiovisual speech

PubMed Central

Romanski, Lizabeth M.

2012-01-01

The integration of facial gestures and vocal signals is an essential process in human communication and relies on an interconnected circuit of brain regions, including language regions in the inferior frontal gyrus (IFG). Studies have determined that ventral prefrontal cortical regions in macaques [e.g., the ventrolateral prefrontal cortex (VLPFC)] share similar cytoarchitectonic features as cortical areas in the human IFG, suggesting structural homology. Anterograde and retrograde tracing studies show that macaque VLPFC receives afferents from the superior and inferior temporal gyrus, which provide complex auditory and visual information, respectively. Moreover, physiological studies have shown that single neurons in VLPFC integrate species-specific face and vocal stimuli. Although bimodal responses may be found across a wide region of prefrontal cortex, vocalization responsive cells, which also respond to faces, are mainly found in anterior VLPFC. This suggests that VLPFC may be specialized to process and integrate social communication information, just as the IFG is specialized to process and integrate speech and gestures in the human brain. PMID:22723356

Shared neural processes support semantic control and action understanding

PubMed Central

Davey, James; Rueschemeyer, Shirley-Ann; Costigan, Alison; Murphy, Nik; Krieger-Redwood, Katya; Hallam, Glyn; Jefferies, Elizabeth

2015-01-01

Executive–semantic control and action understanding appear to recruit overlapping brain regions but existing evidence from neuroimaging meta-analyses and neuropsychology lacks spatial precision; we therefore manipulated difficulty and feature type (visual vs. action) in a single fMRI study. Harder judgements recruited an executive–semantic network encompassing medial and inferior frontal regions (including LIFG) and posterior temporal cortex (including pMTG). These regions partially overlapped with brain areas involved in action but not visual judgements. In LIFG, the peak responses to action and difficulty were spatially identical across participants, while these responses were overlapping yet spatially distinct in posterior temporal cortex. We propose that the co-activation of LIFG and pMTG allows the flexible retrieval of semantic information, appropriate to the current context; this might be necessary both for semantic control and understanding actions. Feature selection in difficult trials also recruited ventral occipital–temporal areas, not implicated in action understanding. PMID:25658631

Effects of childhood trauma on left inferior frontal gyrus function during response inhibition across psychotic disorders.

PubMed

Quidé, Y; O'Reilly, N; Watkeys, O J; Carr, V J; Green, M J

2018-07-01

Childhood trauma is a risk factor for psychosis. Deficits in response inhibition are common to psychosis and trauma-exposed populations, and associated brain functions may be affected by trauma exposure in psychotic disorders. We aimed to identify the influence of trauma-exposure on brain activation and functional connectivity during a response inhibition task. We used functional magnetic resonance imaging to examine brain function within regions-of-interest [left and right inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex, right supplementary motor area, right inferior parietal lobule and dorsal anterior cingulate cortex], during the performance of a Go/No-Go Flanker task, in 112 clinical cases with psychotic disorders and 53 healthy controls (HCs). Among the participants, 71 clinical cases and 21 HCs reported significant levels of childhood trauma exposure, while 41 clinical cases and 32 HCs did not. In the absence of effects on response inhibition performance, childhood trauma exposure was associated with increased activation in the left IFG, and increased connectivity between the left IFG seed region and the cerebellum and calcarine sulcus, in both cases and healthy individuals. There was no main effect of psychosis, and no trauma-by-psychosis interaction for any other region-of-interest. Within the clinical sample, the effects of trauma-exposure on the left IFG activation were mediated by symptom severity. Trauma-related increases in activation of the left IFG were not associated with performance differences, or dependent on clinical diagnostic status; increased IFG functionality may represent a compensatory (overactivation) mechanism required to exert adequate inhibitory control of the motor response.

Cross-frequency coupling in deep brain structures upon processing the painful sensory inputs.

PubMed

Liu, C C; Chien, J H; Kim, J H; Chuang, Y F; Cheng, D T; Anderson, W S; Lenz, F A

2015-09-10

Cross-frequency coupling has been shown to be functionally significant in cortical information processing, potentially serving as a mechanism for integrating functionally relevant regions in the brain. In this study, we evaluate the hypothesis that pain-related gamma oscillatory responses are coupled with low-frequency oscillations in the frontal lobe, amygdala and hippocampus, areas known to have roles in pain processing. We delivered painful laser pulses to random locations on the dorsal hand of five patients with uncontrolled epilepsy requiring depth electrode implantation for seizure monitoring. Two blocks of 40 laser stimulations were delivered to each subject and the pain-intensity was controlled at five in a 0-10 scale by adjusting the energy level of the laser pulses. Local-field-potentials (LFPs) were recorded through bilaterally implanted depth electrode contacts to study the oscillatory responses upon processing the painful laser stimulations. Our results show that painful laser stimulations enhanced low-gamma (LH, 40-70 Hz) and high-gamma (HG, 70-110 Hz) oscillatory responses in the amygdala and hippocampal regions on the right hemisphere and these gamma responses were significantly coupled with the phases of theta (4-7 Hz) and alpha (8-1 2 Hz) rhythms during pain processing. Given the roles of these deep brain structures in emotion, these findings suggest that the oscillatory responses in these regions may play a role in integrating the affective component of pain, which may contribute to our understanding of the mechanisms underlying the affective information processing in humans. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Random Forest Segregation of Drug Responses May Define Regions of Biological Significance

PubMed Central

Bukhari, Qasim; Borsook, David; Rudin, Markus; Becerra, Lino

2016-01-01

The ability to assess brain responses in unsupervised manner based on fMRI measure has remained a challenge. Here we have applied the Random Forest (RF) method to detect differences in the pharmacological MRI (phMRI) response in rats to treatment with an analgesic drug (buprenorphine) as compared to control (saline). Three groups of animals were studied: two groups treated with different doses of the opioid buprenorphine, low (LD), and high dose (HD), and one receiving saline. PhMRI responses were evaluated in 45 brain regions and RF analysis was applied to allocate rats to the individual treatment groups. RF analysis was able to identify drug effects based on differential phMRI responses in the hippocampus, amygdala, nucleus accumbens, superior colliculus, and the lateral and posterior thalamus for drug vs. saline. These structures have high levels of mu opioid receptors. In addition these regions are involved in aversive signaling, which is inhibited by mu opioids. The results demonstrate that buprenorphine mediated phMRI responses comprise characteristic features that allow a supervised differentiation from placebo treated rats as well as the proper allocation to the respective drug dose group using the RF method, a method that has been successfully applied in clinical studies. PMID:27014046

Cortical regions involved in the generation of musical structures during improvisation in pianists.

PubMed

Bengtsson, Sara L; Csíkszentmihályi, Mihály; Ullén, Fredrik

2007-05-01

Studies on simple pseudorandom motor and cognitive tasks have shown that the dorsolateral prefrontal cortex and rostral premotor areas are involved in free response selection. We used functional magnetic resonance imaging to investigate whether these brain regions are also involved in free generation of responses in a more complex creative behavior: musical improvisation. Eleven professional pianists participated in the study. In one condition, Improvise, the pianist improvised on the basis of a visually displayed melody. In the control condition, Reproduce, the participant reproduced his previous improvisation from memory. Participants were able to reproduce their improvisations with a high level of accuracy, and the contrast Improvise versus Reproduce was thus essentially matched in terms of motor output and sensory feedback. However, the Improvise condition required storage in memory of the improvisation. We therefore also included a condition FreeImp, where the pianist improvised but was instructed not to memorize his performance. To locate brain regions involved in musical creation, we investigated the activations in the Improvise-Reproduce contrast that were also present in FreeImp contrasted with a baseline rest condition. Activated brain regions included the right dorsolateral prefrontal cortex, the presupplementary motor area, the rostral portion of the dorsal premotor cortex, and the left posterior part of the superior temporal gyrus. We suggest that these regions are part of a network involved in musical creation, and discuss their possible functional roles.

Plasma and brain angiotensin concentrations associated with water response behavior in the desert anuran, Scaphiopus couchii under natural conditions in the field.

PubMed

Johnson, William E; Hillyard, Stanley D; Propper, Catherine R

2010-12-01

Terrestrial amphibians obtain water by absorption across a specialized region of the ventral skin and exhibit a behavior, the water absorption response (WR) to place that region in contact with moist surfaces. Spadefoot toads (Scaphiopus couchii) spend dry months of the year in burrows, then emerge during brief periods of summer rainfall and seek water sources for rehydration and reproduction. We tested the hypothesis that these toads have changes in plasma and/or central angiotensin concentrations that are associated with seasonal emergence and WR behavior. Immunoreactive concentrations of combined angiotensin II and III (ir-ANG) were measured in plasma samples and microdissected regions of brain tissue taken from toads moving across the road or toads showing WR behavior in shallow puddles on the road. Plasma ir-ANG concentrations were not significantly different between these groups, but were significantly higher in the periventricular region of the hypothalamus in toads showing WR behavior. Concentrations in other brain regions, while highly variable among individuals, were not different between groups. Within the context of the natural history of a specialized desert toad, these results support the hypothesis that ir-ANG is associated with WR behavior in spadefoot toads in a manner analogous to oral drinking exhibited by other vertebrate clades. Copyright © 2010 Elsevier Inc. All rights reserved.

The human parental brain: In vivo neuroimaging

PubMed Central

Swain, James E.

2015-01-01

Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants’ current and future behavior. Indeed, the parent–infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology with parental thoughts and behaviors. After reviewing brain imaging techniques, certain social cognitive and affective concepts are reviewed, including empathy and trust—likely critical to parenting. Following that is a thorough study-by-study review of the state-of-the-art with respect to human neuroimaging studies of the parental brain—from parent brain responses to salient infant stimuli, including emotionally charged baby cries and brief visual stimuli to the latest structural brain studies. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support parental brain responses to infants, including circuits for limbic emotion response and regulation. Thus, a model is presented in which infant stimuli activate sensory analysis brain regions, affect corticolimbic limbic circuits that regulate emotional response, motivation and reward related to their infant, ultimately organizing parenting impulses, thoughts and emotions into coordinated behaviors as a map for future studies. Finally, future directions towards integrated understanding of the brain basis of human parenting are outlined with profound implications for understanding and contributing to long term parent and infant mental health. PMID:21036196

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

PubMed Central

Volkow, Nora D.; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S.; Alexoff, David; Logan, Jean; Jayne, Millard; Wong, Christopher; Tomasi, Dardo

2014-01-01

Moves to legalize marijuana highlight the urgency to investigate effects of chronic marijuana in the human brain. Here, we challenged 48 participants (24 controls and 24 marijuana abusers) with methylphenidate (MP), a drug that elevates extracellular dopamine (DA) as a surrogate for probing the reactivity of the brain to DA stimulation. We compared the subjective, cardiovascular, and brain DA responses (measured with PET and [11C]raclopride) to MP between controls and marijuana abusers. Although baseline (placebo) measures of striatal DA D2 receptor availability did not differ between groups, the marijuana abusers showed markedly blunted responses when challenged with MP. Specifically, compared with controls, marijuana abusers had significantly attenuated behavioral (“self-reports” for high, drug effects, anxiety, and restlessness), cardiovascular (pulse rate and diastolic blood pressure), and brain DA [reduced decreases in distribution volumes (DVs) of [11C]raclopride, although normal reductions in striatal nondisplaceable binding potential (BPND)] responses to MP. In ventral striatum (key brain reward region), MP-induced reductions in DVs and BPND (reflecting DA increases) were inversely correlated with scores of negative emotionality, which were significantly higher for marijuana abusers than controls. In marijuana abusers, DA responses in ventral striatum were also inversely correlated with addiction severity and craving. The attenuated responses to MP, including reduced decreases in striatal DVs, are consistent with decreased brain reactivity to the DA stimulation in marijuana abusers that might contribute to their negative emotionality (increased stress reactivity and irritability) and addictive behaviors. PMID:25024177

Tinnitus and hyperacusis: Contributions of paraflocculus, reticular formation and stress.

PubMed

Chen, Yu-Chen; Chen, Guang-Di; Auerbach, Benjamin D; Manohar, Senthilvelan; Radziwon, Kelly; Salvi, Richard

2017-06-01

Tinnitus and hyperacusis are common and potentially serious hearing disorders associated with noise-, age- or drug-induced hearing loss. Accumulating evidence suggests that tinnitus and hyperacusis are linked to excessive neural activity in a distributed brain network that not only includes the central auditory pathway, but also brain regions involved in arousal, emotion, stress and motor control. Here we examine electrophysiological changes in two novel non-auditory areas implicated in tinnitus and hyperacusis: the caudal pontine reticular nucleus (PnC), involved in arousal, and the paraflocculus lobe of the cerebellum (PFL), implicated in head-eye coordination and gating tinnitus and we measure the changes in corticosterone stress hormone levels. Using the salicylate-induced model of tinnitus and hyperacusis, we found that long-latency (>10 ms) sound-evoked response components in both the brain regions were significantly enhanced after salicylate administration, while the short-latency responses were reduced, likely reflecting cochlear hearing loss. These results are consistent with the central gain model of tinnitus and hyperacusis, which proposes that these disorders arise from the amplification of neural activity in central auditory pathway plus other regions linked to arousal, emotion, tinnitus gating and motor control. Finally, we demonstrate that salicylate results in an increase in corticosterone level in a dose-dependent manner consistent with the notion that stress may interact with hearing loss in tinnitus and hyperacusis development. This increased stress response has the potential to have wide-ranging effects on the central nervous system and may therefore contribute to brain-wide changes in neural activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Connectivity Predicts Deep Brain Stimulation Outcome in Parkinson Disease

PubMed Central

Horn, Andreas; Reich, Martin; Vorwerk, Johannes; Li, Ningfei; Wenzel, Gregor; Fang, Qianqian; Schmitz-Hübsch, Tanja; Nickl, Robert; Kupsch, Andreas; Volkmann, Jens; Kühn, Andrea A.; Fox, Michael D.

2018-01-01

Objective The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. Methods A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. Results In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p<0.001). This same connectivity profile predicted response in an independent patient cohort (p<0.01). Structural and functional connectivity were independent predictors of clinical improvement (p<0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. Interpretation Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. PMID:28586141

Central autonomic network mediates cardiovascular responses to acute inflammation: Relevance to increased cardiovascular risk in depression?

PubMed Central

Harrison, Neil A.; Cooper, Ella; Voon, Valerie; Miles, Ken; Critchley, Hugo D.

2013-01-01

Inflammation is a risk factor for both depression and cardiovascular disease. Depressed mood is also a cardiovascular risk factor. To date, research into mechanisms through which inflammation impacts cardiovascular health rarely takes into account central effects on autonomic cardiovascular control, instead emphasizing direct effects of peripheral inflammatory responses on endothelial reactivity and myocardial function. However, brain responses to inflammation engage neural systems for motivational and homeostatic control and are expressed through depressed mood state and changes in autonomic cardiovascular regulation. Here we combined an inflammatory challenge, known to evoke an acute reduction in mood, with neuroimaging to identify the functional brain substrates underlying potentially detrimental changes in autonomic cardiovascular control. We first demonstrated that alterations in the balance of low to high frequency (LF/HF) changes in heart rate variability (a measure of baroreflex sensitivity) could account for some of the inflammation-evoked changes in diastolic blood pressure, indicating a central (rather than solely local endothelial) origin. Accompanying alterations in regional brain metabolism (measured using 18FDG-PET) were analysed to localise central mechanisms of inflammation-induced changes in cardiovascular state: three discrete regions previously implicated in stressor-evoked blood pressure reactivity, the dorsal anterior and posterior cingulate and pons, strongly mediated the relationship between inflammation and blood pressure. Moreover, activity changes within each region predicted the inflammation-induced shift in LF/HF balance. These data are consistent with a centrally-driven component originating within brain areas supporting stressor evoked blood pressure reactivity. Together our findings highlight mechanisms binding psychological and physiological well-being and their perturbation by peripheral inflammation. PMID:23416033

Stimuli and consequences of dendritic release of oxytocin within the brain.

PubMed

Neumann, I D

2007-11-01

The brain oxytocin system has served as a distinguished model system in neuroendocrinology to study detailed mechanisms of intracerebral release, in particular of somatodendritic release, and its behavioural and neuroendocrine consequences. It has been shown that oxytocin is released within various brain regions, but evidence for dendritic release is limited to the main sites of oxytocin synthesis, i.e. the hypothalamic SON (supraoptic nucleus) and PVN (paraventricular nucleus). In the present paper, stimuli of dendritic release of oxytocin and the related neuropeptide vasopressin are discussed, including parturition and suckling, i.e. the period of a highly activated brain oxytocin system. Also, exposure to various pharmacological, psychological or physical stressors triggers dendritic oxytocin release, as monitored by intracerebral microdialysis within the SON and PVN during ongoing behavioural testing. So far, dendritic release of the neuropeptide has only been demonstrated within the hypothalamus, but intracerebral oxytocin release has also been found within the central amygdala and the septum in response to various stimuli including stressor exposure. Such a locally released oxytocin modulates physiological and behavioural reproductive functions, emotionality and hormonal stress responses, as it exerts, for example, pro-social, anxiolytic and antistress actions within restricted brain regions. These discoveries make oxytocin a promising neuromodulator of the brain for psychotherapeutic intervention and treatment of numerous psychiatric illnesses, for example, anxiety-related diseases, social phobia, autism and postpartum depression.

Brain response to images of food varying in energy density is associated with body composition in 7- to 10-year-old children: Results of an exploratory study.

PubMed

Fearnbach, S Nicole; English, Laural K; Lasschuijt, Marlou; Wilson, Stephen J; Savage, Jennifer S; Fisher, Jennifer O; Rolls, Barbara J; Keller, Kathleen L

2016-08-01

Energy balance is regulated by a multifaceted system of physiological signals that influence energy intake and expenditure. Therefore, variability in the brain's response to food may be partially explained by differences in levels of metabolically active tissues throughout the body, including fat-free mass (FFM) and fat mass (FM). The purpose of this study was to test the hypothesis that children's body composition would be related to their brain response to food images varying in energy density (ED), a measure of energy content per weight of food. Functional magnetic resonance imaging (fMRI) was used to measure brain response to High (>1.5kcal/g) and Low (<1.5kcal/g) ED food images, and Control images, in 36 children ages 7-10years. Body composition was measured using bioelectrical impedance analysis. Multi-subject random effects general linear model (GLM) and two-factor repeated measures analysis of variance (ANOVA) were used to test for main effects of ED (High ED vs. Low ED) in a priori defined brain regions of interest previously implicated in energy homeostasis and reward processing. Pearson's correlations were then calculated between activation in these regions for various contrasts (High ED-Low ED, High ED-Control, Low ED-Control) and child body composition (FFM index, FM index, % body fat). Relative to Low ED foods, High ED foods elicited greater BOLD activation in the left thalamus. In the right substantia nigra, BOLD activation for the contrast of High ED-Low ED foods was positively associated with child FFM. There were no significant results for the High ED-Control or Low ED-Control contrasts. Our findings support literature on FFM as an appetitive driver, such that greater amounts of lean mass were associated with greater activation for High ED foods in an area of the brain associated with dopamine signaling and reward (substantia nigra). These results confirm our hypothesis that brain response to foods varying in energy content is related to measures of child body composition. Copyright © 2016 Elsevier Inc. All rights reserved.

Decoding Pedophilia: Increased Anterior Insula Response to Infant Animal Pictures

PubMed Central

Ponseti, Jorge; Bruhn, Daniel; Nolting, Julia; Gerwinn, Hannah; Pohl, Alexander; Stirn, Aglaja; Granert, Oliver; Laufs, Helmut; Deuschl, Günther; Wolff, Stephan; Jansen, Olav; Siebner, Hartwig; Briken, Peer; Mohnke, Sebastian; Amelung, Till; Kneer, Jonas; Schiffer, Boris; Walter, Henrik; Kruger, Tillmann H. C.

2018-01-01

Previous research found increased brain responses of men with sexual interest in children (i.e., pedophiles) not only to pictures of naked children but also to pictures of child faces. This opens the possibly that pedophilia is linked (in addition to or instead of an aberrant sexual system) to an over-active nurturing system. To test this hypothesis we exposed pedophiles and healthy controls to pictures of infant and adult animals during functional magnetic resonance imaging of the brain. By using pictures of infant animals (instead of human infants), we aimed to elicit nurturing processing without triggering sexual processing. We hypothesized that elevated brain responses to nurturing stimuli will be found – in addition to other brain areas – in the anterior insula of pedophiles because this area was repeatedly found to be activated when adults see pictures of babies. Behavioral ratings confirmed that pictures of infant or adult animals were not perceived as sexually arousing neither by the pedophilic participants nor by the heathy controls. Statistical analysis was applied to the whole brain as well as to the anterior insula as region of interest. Only in pedophiles did infants relative to adult animals increase brain activity in the anterior insula, supplementary motor cortex, and dorsolateral prefrontal areas. Within-group analysis revealed an increased brain response to infant animals in the left anterior insular cortex of the pedophilic participants. Currently, pedophilia is considered the consequence of disturbed sexual or executive brain processing, but details are far from known. The present findings raise the question whether there is also an over-responsive nurturing system in pedophilia. PMID:29403367

Decoding Pedophilia: Increased Anterior Insula Response to Infant Animal Pictures.

PubMed

Ponseti, Jorge; Bruhn, Daniel; Nolting, Julia; Gerwinn, Hannah; Pohl, Alexander; Stirn, Aglaja; Granert, Oliver; Laufs, Helmut; Deuschl, Günther; Wolff, Stephan; Jansen, Olav; Siebner, Hartwig; Briken, Peer; Mohnke, Sebastian; Amelung, Till; Kneer, Jonas; Schiffer, Boris; Walter, Henrik; Kruger, Tillmann H C

2017-01-01

Previous research found increased brain responses of men with sexual interest in children (i.e., pedophiles) not only to pictures of naked children but also to pictures of child faces. This opens the possibly that pedophilia is linked (in addition to or instead of an aberrant sexual system) to an over-active nurturing system. To test this hypothesis we exposed pedophiles and healthy controls to pictures of infant and adult animals during functional magnetic resonance imaging of the brain. By using pictures of infant animals (instead of human infants), we aimed to elicit nurturing processing without triggering sexual processing. We hypothesized that elevated brain responses to nurturing stimuli will be found - in addition to other brain areas - in the anterior insula of pedophiles because this area was repeatedly found to be activated when adults see pictures of babies. Behavioral ratings confirmed that pictures of infant or adult animals were not perceived as sexually arousing neither by the pedophilic participants nor by the heathy controls. Statistical analysis was applied to the whole brain as well as to the anterior insula as region of interest. Only in pedophiles did infants relative to adult animals increase brain activity in the anterior insula, supplementary motor cortex, and dorsolateral prefrontal areas. Within-group analysis revealed an increased brain response to infant animals in the left anterior insular cortex of the pedophilic participants. Currently, pedophilia is considered the consequence of disturbed sexual or executive brain processing, but details are far from known. The present findings raise the question whether there is also an over-responsive nurturing system in pedophilia.

Neuroimaging of response interference in twins concordant or discordant for inattention and hyperactivity symptoms

PubMed Central

van ’t Ent, D.; van Beijsterveldt, C.E.M.; Derks, E.M.; Hudziak, J.J.; Veltman, D.J.; Todd, R.D.; Boomsma, D.I.; De Geus, E.J.C.

2009-01-01

Attention deficit hyperactivity disorder (ADHD) is to a large extent influenced by genetic factors, but environmental influences are considered important as well. To distinguish between functional brain changes underlying primarily genetically and environmentally mediated ADHD, we used functional MRI to compare response interference in monozygotic twins highly concordant or discordant for attention problems (AP). AP scores were assessed longitudinally with the Child Behavior Check List attention problem scale (CBCL-AP). Response interference was measured during two executive function paradigms; a color-word Stroop and a flanker task. The neuroimaging results indicated that, across the entire sample, children with high CBCL-AP scores, relative to children with low CBCL-AP scores, showed decreased activation to response interference in dorsolateral prefrontal, parietal and temporal brain regions. Increased activation was noted in the premotor cortex and regions associated with visual selective attention processing, possibly reflecting compensatory mechanisms to maintain task performance. Specific comparisons of high and low scoring concordant twin pairs suggest that AP of genetic origin was characterized by decreased activation of the left dorsolateral prefrontal cortex during the Stroop task and right parietal lobe during the flanker task. In contrast, comparison of twins from discordant monozygotic pairs, suggest that AP of environmental origin was characterized by decreased activation in left and right temporal lobe areas, but only during Stroop interference. The finding of distinct brain activation changes to response interference in inattention/hyperactivity of ‘genetic’ versus ‘environmental’ origin, indicate that genetic and environmental risk factors for attention/hyperactivity problems affect the brain in different ways. PMID:19409224

Role of CD4+ T cells in a protective immune response against Cryptococcus neoformans in the central nervous system.

PubMed

Uicker, William C; McCracken, James P; Buchanan, Kent L

2006-02-01

Cryptococcosis is a life-threatening disease caused by the encapsulated yeast, Cryptococcus neoformans. Although infection with C. neoformans is initiated in the lungs, morbidity and mortality is mostly associated with infections of the central nervous system (CNS). Individuals with deficiencies in cell-mediated immunity, such as patients with AIDS, are more susceptible to disseminated cryptococcosis, highlighting the importance of cell-mediated immunity and CD4+ T cells in host resistance against C. neoformans. Using a mouse model of cryptococcal meningoencephalitis, we have shown that immunization of mice with a cryptococcal antigen induced a protective immune response that crossed the blood-brain barrier and initiated an immune response directly in the CNS if C. neoformans was present. The regional protective response was characteristic of a Type-1 (Th1) response in the types of cells present at the site of infection and in the cytokines and chemokines expressed. Here, we extend those findings and report that CD4+ T cells are required for survival of immune mice infected directly in the brain with C. neoformans and sensitized CD4 + T cells can transfer partial protection to naive mice infected intracerebrally with C. neoformans. Furthermore, CD4 + T cells were also important for optimal infiltration of inflammatory cells at the site of infection and in the expression of cytokines and chemokines associated with protection in the brain. Lastly, CD4+ T cells were required for optimal regional production and secretion of IFNgamma and in the significantly increased expression of iNOS in C. neoformans-infected brains of immune mice.

Does Watching a Play about the Teenage Brain Affect Attitudes toward Young Offenders?

PubMed Central

Blakey, Robert

2017-01-01

Neuroscience is increasingly used to infer the cognitive capacities of offenders from the activity and volume of different brain regions, with the resultant findings receiving great interest in the public eye. This field experiment tested the effects of public engagement in neuroscience on attitudes toward offenders. Brainstorm is a play about teenage brain development. Either before or after watching this play, 728 participants responded to four questions about the age of criminal responsibility, and the moral responsibility and dangerousness of a hypothetical young or adult offender. After watching the play, participants perceived the young offender as less likely to reoffend than the adult offender and the young, but not adult, offender as less morally responsible for his actions, especially on the first offense. Therefore, public engagement in the newest arrival to the criminological scene – neuroscience – may shift support for different youth justice responses. PMID:28649215

A Direct Brain-to-Brain Interface in Humans

PubMed Central

Rao, Rajesh P. N.; Stocco, Andrea; Bryan, Matthew; Sarma, Devapratim; Youngquist, Tiffany M.; Wu, Joseph; Prat, Chantel S.

2014-01-01

We describe the first direct brain-to-brain interface in humans and present results from experiments involving six different subjects. Our non-invasive interface, demonstrated originally in August 2013, combines electroencephalography (EEG) for recording brain signals with transcranial magnetic stimulation (TMS) for delivering information to the brain. We illustrate our method using a visuomotor task in which two humans must cooperate through direct brain-to-brain communication to achieve a desired goal in a computer game. The brain-to-brain interface detects motor imagery in EEG signals recorded from one subject (the “sender”) and transmits this information over the internet to the motor cortex region of a second subject (the “receiver”). This allows the sender to cause a desired motor response in the receiver (a press on a touchpad) via TMS. We quantify the performance of the brain-to-brain interface in terms of the amount of information transmitted as well as the accuracies attained in (1) decoding the sender’s signals, (2) generating a motor response from the receiver upon stimulation, and (3) achieving the overall goal in the cooperative visuomotor task. Our results provide evidence for a rudimentary form of direct information transmission from one human brain to another using non-invasive means. PMID:25372285

Brain lactate responses during visual stimulation in fasting and hyperglycemic subjects: a proton magnetic resonance spectroscopy study at 1.5 Tesla.

PubMed

Maddock, Richard J; Buonocore, Michael H; Lavoie, Shawn P; Copeland, Linda E; Kile, Shawn J; Richards, Anne L; Ryan, John M

2006-11-22

Proton magnetic resonance spectroscopy ((1)H-MRS) studies showing increased lactate during neural activation support a broader role for lactate in brain energy metabolism than was traditionally recognized. Proton MRS measures of brain lactate responses have been used to study regional brain metabolism in clinical populations. This study examined whether variations in blood glucose influence the lactate response to visual stimulation in the visual cortex. Six subjects were scanned twice, receiving either saline or 21% glucose intravenously. Using (1)H-MRS at 1.5 Tesla with a long echo time (TE=288 ms), the lactate doublet was visible at 1.32 ppm in the visual cortex of all subjects. Lactate increased significantly from resting to visual stimulation. Hyperglycemia had no effect on this increase. The order of the slice-selective gradients for defining the spectroscopy voxel had a pronounced effect on the extent of contamination by signal originating outside the voxel. The results of this preliminary study demonstrate a method for observing a consistent activity-stimulated increase in brain lactate at 1.5 T and show that variations in blood glucose across the normal range have little effect on this response.

How real-life health messages engage our brains: Shared processing of effective anti-alcohol videos

PubMed Central

Schmälzle, Ralf; Renner, Britta; Schupp, Harald T.

2017-01-01

Abstract Health communication via mass media is an important strategy when targeting risky drinking, but many questions remain about how health messages are processed and how they unfold their effects within receivers. Here we examine how the brains of young adults—a key target group for alcohol prevention—‘tune in’ to real-life health prevention messages about risky alcohol use. In a first study, a large sample of authentic public service announcements (PSAs) targeting the risks of alcohol was characterized using established measures of message effectiveness. In the main study, we used inter-subject correlation analysis of fMRI data to examine brain responses to more and less effective PSAs in a sample of young adults. We find that more effective messages command more similar responses within widespread brain regions, including the dorsomedial prefrontal cortex, insulae and precuneus. In previous research, these regions have been related to processing narratives, emotional stimuli, self-relevance and attention towards salient stimuli. The present study thus suggests that more effective health prevention messages have greater ‘neural reach’, i.e. they engage the brains of audience members’ more widely. This work outlines a promising strategy for assessing the effects of health communication at a neural level. PMID:28402568

How real-life health messages engage our brains: Shared processing of effective anti-alcohol videos.

PubMed

Imhof, Martin A; Schmälzle, Ralf; Renner, Britta; Schupp, Harald T

2017-07-01

Health communication via mass media is an important strategy when targeting risky drinking, but many questions remain about how health messages are processed and how they unfold their effects within receivers. Here we examine how the brains of young adults-a key target group for alcohol prevention-'tune in' to real-life health prevention messages about risky alcohol use. In a first study, a large sample of authentic public service announcements (PSAs) targeting the risks of alcohol was characterized using established measures of message effectiveness. In the main study, we used inter-subject correlation analysis of fMRI data to examine brain responses to more and less effective PSAs in a sample of young adults. We find that more effective messages command more similar responses within widespread brain regions, including the dorsomedial prefrontal cortex, insulae and precuneus. In previous research, these regions have been related to processing narratives, emotional stimuli, self-relevance and attention towards salient stimuli. The present study thus suggests that more effective health prevention messages have greater 'neural reach', i.e. they engage the brains of audience members' more widely. This work outlines a promising strategy for assessing the effects of health communication at a neural level. © The Author (2017). Published by Oxford University Press.

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders.

PubMed

Sato, Wataru; Toichi, Motomi; Uono, Shota; Kochiyama, Takanori

2012-08-13

Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD.We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex-MTG-IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.

Brain Responses to High-Protein Diets12

PubMed Central

Journel, Marion; Chaumontet, Catherine; Darcel, Nicolas; Fromentin, Gilles; Tomé, Daniel

2012-01-01

Proteins are suspected to have a greater satiating effect than the other 2 macronutrients. After protein consumption, peptide hormones released from the gastrointestinal tract (mainly anorexigenic gut peptides such as cholecystokinin, glucagon peptide 1, and peptide YY) communicate information about the energy status to the brain. These hormones and vagal afferents control food intake by acting on brain regions involved in energy homeostasis such as the brainstem and the hypothalamus. In fact, a high-protein diet leads to greater activation than a normal-protein diet in the nucleus tractus solitarius and in the arcuate nucleus. More specifically, neural mechanisms triggered particularly by leucine consumption involve 2 cellular energy sensors: the mammalian target of rapamycin and AMP-activated protein kinase. In addition, reward and motivation aspects of eating behavior, controlled mainly by neurons present in limbic regions, play an important role in the reduced hedonic response of a high-protein diet. This review examines how metabolic signals emanating from the gastrointestinal tract after protein ingestion target the brain to control feeding, energy expenditure, and hormones. Understanding the functional roles of brain areas involved in the satiating effect of proteins and their interactions will demonstrate how homeostasis and reward are integrated with the signals from peripheral organs after protein consumption. PMID:22585905

Neural signatures of third-party punishment: evidence from penetrating traumatic brain injury

PubMed Central

Glass, Leila; Moody, Lara; Grafman, Jordan

2016-01-01

The ability to survive within a cooperative society depends on impartial third-party punishment (TPP) of social norm violations. Two cognitive mechanisms have been postulated as necessary for the successful completion of TPP: evaluation of legal responsibility and selection of a suitable punishment given the magnitude of the crime. Converging neuroimaging research suggests two supporting domain-general networks; a mentalizing network for evaluation of legal responsibility and a central-executive network for determination of punishment. A whole-brain voxel-based lesion-symptom mapping approach was used in conjunction with a rank-order TPP task to identify brain regions necessary for TPP in a large sample of patients with penetrating traumatic brain injury. Patients who demonstrated atypical TPP had specific lesions in core regions of the mentalizing (dorsomedial prefrontal cortex [PFC], ventromedial PFC) and central-executive (bilateral dorsolateral PFC, right intraparietal sulcus) networks. Altruism and executive functioning (concept formation skills) were significant predictors of TPP: altruism was uniquely associated with TPP in patients with lesions in right dorsolateral PFC and executive functioning was uniquely associated with TPP in individuals with lesions in left PFC. Our findings contribute to the extant literature to support underlying neural networks associated with TPP, with specific brain-behavior causal relationships confirming recent functional neuroimaging research. PMID:26276809

Dynamical properties of the brain tissue under oscillatory shear stresses at large strain range

NASA Astrophysics Data System (ADS)

Boudjema, F.; Khelidj, B.; Lounis, M.

2017-01-01

In this experimental work, we study the viscoelastic behaviour of in vitro brain tissue, particularly the white matter, under oscillatory shear strain. The selective vulnerability of this tissue is the anisotropic mechanical properties of theirs different regions lead to a sensitivity to the angular shear rate and magnitude of strain. For this aim, shear storage modulus (G‧) and loss modulus (G″) were measured over a range of frequencies (1 to 100 Hz), for different levels of strain (1 %, to 50 %). The mechanical responses of the brain matter samples showed a viscoelastic behaviour that depend on the correlated strain level and frequency range and old age sample. The samples have been showed evolution behaviour by increasing then decreasing the strain level. Also, the stiffness anisotropy of brain matter was showed between regions and species.

Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli

PubMed Central

Hasen, Nina S.; Gammie, Stephen C.

2010-01-01

The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2-/- knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female. PMID:21070815

Retrieval Search and Strength Evoke Dissociable Brain Activity during Episodic Memory Recall

PubMed Central

Reas, Emilie T.; Brewer, James B.

2014-01-01

Neuroimaging studies of episodic memory retrieval have revealed activations in the human frontal, parietal, and medial-temporal lobes that are associated with memory strength. However, it remains unclear whether these brain responses are veritable signals of memory strength or are instead regulated by concomitant subcomponents of retrieval such as retrieval effort or mental search. This study used event-related fMRI during cued recall of previously memorized word-pair associates to dissociate brain responses modulated by memory search from those modulated by the strength of a recalled memory. Search-related deactivations, dissociated from activity due to memory strength, were observed in regions of the default network, whereas distinctly strength-dependent activations were present in superior and inferior parietal and dorsolateral PFC. Both search and strength regulated activity in dorsal anterior cingulate and anterior insula. These findings suggest that, although highly correlated and partially subserved by overlapping cognitive control mechanisms, search and memory strength engage dissociable regions of frontoparietal attention and default networks. PMID:23190328

Distinct frontal regions subserve evaluation of linguistic and emotional aspects of speech intonation.

PubMed

Wildgruber, D; Hertrich, I; Riecker, A; Erb, M; Anders, S; Grodd, W; Ackermann, H

2004-12-01

In addition to the propositional content of verbal utterances, significant linguistic and emotional information is conveyed by the tone of speech. To differentiate brain regions subserving processing of linguistic and affective aspects of intonation, discrimination of sentences differing in linguistic accentuation and emotional expressiveness was evaluated by functional magnetic resonance imaging. Both tasks yielded rightward lateralization of hemodynamic responses at the level of the dorsolateral frontal cortex as well as bilateral thalamic and temporal activation. Processing of linguistic and affective intonation, thus, seems to be supported by overlapping neural networks comprising partially right-sided brain regions. Comparison of hemodynamic activation during the two different tasks, however, revealed bilateral orbito-frontal responses restricted to the affective condition as opposed to activation of the left lateral inferior frontal gyrus confined to evaluation of linguistic intonation. These findings indicate that distinct frontal regions contribute to higher level processing of intonational information depending on its communicational function. In line with other components of language processing, discrimination of linguistic accentuation seems to be lateralized to the left inferior-lateral frontal region whereas bilateral orbito-frontal areas subserve evaluation of emotional expressiveness.

Multiscale energy reallocation during low-frequency steady-state brain response.

PubMed

Wang, Yifeng; Chen, Wang; Ye, Liangkai; Biswal, Bharat B; Yang, Xuezhi; Zou, Qijun; Yang, Pu; Yang, Qi; Wang, Xinqi; Cui, Qian; Duan, Xujun; Liao, Wei; Chen, Huafu

2018-05-01

Traditional task-evoked brain activations are based on detection and estimation of signal change from the mean signal. By contrast, the low-frequency steady-state brain response (lfSSBR) reflects frequency-tagging activity at the fundamental frequency of the task presentation and its harmonics. Compared to the activity at these resonant frequencies, brain responses at nonresonant frequencies are largely unknown. Additionally, because the lfSSBR is defined by power change, we hypothesize using Parseval's theorem that the power change reflects brain signal variability rather than the change of mean signal. Using a face recognition task, we observed power increase at the fundamental frequency (0.05 Hz) and two harmonics (0.1 and 0.15 Hz) and power decrease within the infra-slow frequency band (<0.1 Hz), suggesting a multifrequency energy reallocation. The consistency of power and variability was demonstrated by the high correlation (r > .955) of their spatial distribution and brain-behavior relationship at all frequency bands. Additionally, the reallocation of finite energy was observed across various brain regions and frequency bands, forming a particular spatiotemporal pattern. Overall, results from this study strongly suggest that frequency-specific power and variability may measure the same underlying brain activity and that these results may shed light on different mechanisms between lfSSBR and brain activation, and spatiotemporal characteristics of energy reallocation induced by cognitive tasks. © 2018 Wiley Periodicals, Inc.

Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression

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

Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M.

Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP – a marker of neuronal activation – in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing “helpless” behavior had an overall brain-wide reduction in the level ofmore » neuronal activation compared with mice showing “resilient” behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. In conclusion, our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses tostress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.« less

Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression

DOE PAGES

Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M.; ...

2016-02-03

Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP – a marker of neuronal activation – in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing “helpless” behavior had an overall brain-wide reduction in the level ofmore » neuronal activation compared with mice showing “resilient” behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. In conclusion, our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses tostress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.« less

Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression

PubMed Central

Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M.; Pradhan, Kith; Henn, Fritz A.; Shea, Stephen; Osten, Pavel; Li, Bo

2016-01-01

Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP – a marker of neuronal activation – in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing “helpless” behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing “resilient” behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses. PMID:26869888

Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats.

PubMed

Iyyaswamy, Ashok; Rathinasamy, Sheeladevi

2012-09-01

This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

Region-specific differences in bioenergetic proteins and protein response to acute high fat diet in brains of low and high capacity runner rats.

PubMed

Gan, Li; Ma, Delin; Li, Min; Yang, Fu-Chen; Rogers, Robert S; Wheatley, Joshua L; Koch, Lauren G; Britton, Steven L; Thyfault, John P; Geiger, Paige C; Stanford, John A

2018-05-01

Aerobic capacity is a strong predictor of mortality. Low capacity runner (LCR) rats exhibit reduced mitochondrial function in peripheral organs. A high fat diet (HFD) can worsen metabolic phenotype in LCR rats. Little is known about metabolic changes in the brains of these rats, however. This study examined protein markers of mitochondrial function and metabolism as a function of aerobic running capacity and an acute HFD in four brain regions: the striatum, hippocampus, hypothalamus, and substantia nigra. After 3 days HFD or chow diets, we measured peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1-α), nuclear respiratory factors 1 (Nrf-1), mitochondrial transcription factor A (TFAM), and phosphorylated (activated) AMP-activated protein kinase (p-AMPK) protein levels in the four brain regions. LCR rats exhibited lower levels of mitochondrial proteins (PGC1-α, Nrf-1, TFAM), and greater p-AMPK, in striatum, but not in the other brain regions. Mitochondrial protein levels were greater in HFD LCR striatum, while p-AMPK was lower in this group. Markers of lower mitochondrial biogenesis and increased metabolic demand were limited to the LCR striatum, which nevertheless maintained the capacity to respond to an acute HFD challenge. Copyright © 2018 Elsevier B.V. All rights reserved.

The association between resting functional connectivity and dispositional optimism.

PubMed

Ran, Qian; Yang, Junyi; Yang, Wenjing; Wei, Dongtao; Qiu, Jiang; Zhang, Dong

2017-01-01

Dispositional optimism is an individual characteristic that plays an important role in human experience. Optimists are people who tend to hold positive expectations for their future. Previous studies have focused on the neural basis of optimism, such as task response neural activity and brain structure volume. However, the functional connectivity between brain regions of the dispositional optimists are poorly understood. Previous study suggested that the ventromedial prefrontal cortex (vmPFC) are associated with individual differences in dispositional optimism, but it is unclear whether there are other brain regions that combine with the vmPFC to contribute to dispositional optimism. Thus, the present study used the resting-state functional connectivity (RSFC) approach and set the vmPFC as the seed region to examine if differences in functional brain connectivity between the vmPFC and other brain regions would be associated with individual differences in dispositional optimism. The results found that dispositional optimism was significantly positively correlated with the strength of the RSFC between vmPFC and middle temporal gyrus (mTG) and negativly correlated with RSFC between vmPFC and inferior frontal gyrus (IFG). These findings may be suggested that mTG and IFG which associated with emotion processes and emotion regulation also play an important role in the dispositional optimism.

The association between resting functional connectivity and dispositional optimism

PubMed Central

Yang, Wenjing; Wei, Dongtao; Qiu, Jiang; Zhang, Dong

2017-01-01

Dispositional optimism is an individual characteristic that plays an important role in human experience. Optimists are people who tend to hold positive expectations for their future. Previous studies have focused on the neural basis of optimism, such as task response neural activity and brain structure volume. However, the functional connectivity between brain regions of the dispositional optimists are poorly understood. Previous study suggested that the ventromedial prefrontal cortex (vmPFC) are associated with individual differences in dispositional optimism, but it is unclear whether there are other brain regions that combine with the vmPFC to contribute to dispositional optimism. Thus, the present study used the resting-state functional connectivity (RSFC) approach and set the vmPFC as the seed region to examine if differences in functional brain connectivity between the vmPFC and other brain regions would be associated with individual differences in dispositional optimism. The results found that dispositional optimism was significantly positively correlated with the strength of the RSFC between vmPFC and middle temporal gyrus (mTG) and negativly correlated with RSFC between vmPFC and inferior frontal gyrus (IFG). These findings may be suggested that mTG and IFG which associated with emotion processes and emotion regulation also play an important role in the dispositional optimism. PMID:28700613

Enhancing Motor Network Activity Using Real-Time Functional MRI Neurofeedback of Left Premotor Cortex

PubMed Central

Marins, Theo F.; Rodrigues, Erika C.; Engel, Annerose; Hoefle, Sebastian; Basílio, Rodrigo; Lent, Roberto; Moll, Jorge; Tovar-Moll, Fernanda

2015-01-01

Neurofeedback by functional magnetic resonance imaging (fMRI) is a technique of potential therapeutic relevance that allows individuals to be aware of their own neurophysiological responses and to voluntarily modulate the activity of specific brain regions, such as the premotor cortex (PMC), important for motor recovery after brain injury. We investigated (i) whether healthy human volunteers are able to up-regulate the activity of the left PMC during a right hand finger tapping motor imagery (MI) task while receiving continuous fMRI-neurofeedback, and (ii) whether successful modulation of brain activity influenced non-targeted motor control regions. During the MI task, participants of the neurofeedback group (NFB) received ongoing visual feedback representing the level of fMRI responses within their left PMC. Control (CTL) group participants were shown similar visual stimuli, but these were non-contingent on brain activity. Both groups showed equivalent levels of behavioral ratings on arousal and MI, before and during the fMRI protocol. In the NFB, but not in CLT group, brain activation during the last run compared to the first run revealed increased activation in the left PMC. In addition, the NFB group showed increased activation in motor control regions extending beyond the left PMC target area, including the supplementary motor area, basal ganglia and cerebellum. Moreover, in the last run, the NFB group showed stronger activation in the left PMC/inferior frontal gyrus when compared to the CTL group. Our results indicate that modulation of PMC and associated motor control areas can be achieved during a single neurofeedback-fMRI session. These results contribute to a better understanding of the underlying mechanisms of MI-based neurofeedback training, with direct implications for rehabilitation strategies in severe brain disorders, such as stroke. PMID:26733832

Inter-subject synchronization of brain responses during natural music listening.

PubMed

Abrams, Daniel A; Ryali, Srikanth; Chen, Tianwen; Chordia, Parag; Khouzam, Amirah; Levitin, Daniel J; Menon, Vinod

2013-05-01

Music is a cultural universal and a rich part of the human experience. However, little is known about common brain systems that support the processing and integration of extended, naturalistic 'real-world' music stimuli. We examined this question by presenting extended excerpts of symphonic music, and two pseudomusical stimuli in which the temporal and spectral structure of the Natural Music condition were disrupted, to non-musician participants undergoing functional brain imaging and analysing synchronized spatiotemporal activity patterns between listeners. We found that music synchronizes brain responses across listeners in bilateral auditory midbrain and thalamus, primary auditory and auditory association cortex, right-lateralized structures in frontal and parietal cortex, and motor planning regions of the brain. These effects were greater for natural music compared to the pseudo-musical control conditions. Remarkably, inter-subject synchronization in the inferior colliculus and medial geniculate nucleus was also greater for the natural music condition, indicating that synchronization at these early stages of auditory processing is not simply driven by spectro-temporal features of the stimulus. Increased synchronization during music listening was also evident in a right-hemisphere fronto-parietal attention network and bilateral cortical regions involved in motor planning. While these brain structures have previously been implicated in various aspects of musical processing, our results are the first to show that these regions track structural elements of a musical stimulus over extended time periods lasting minutes. Our results show that a hierarchical distributed network is synchronized between individuals during the processing of extended musical sequences, and provide new insight into the temporal integration of complex and biologically salient auditory sequences. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Leptin Is Associated With Exaggerated Brain Reward and Emotion Responses to Food Images in Adolescent Obesity

PubMed Central

Jastreboff, Ania M.; Lacadie, Cheryl; Seo, Dongju; Kubat, Jessica; Van Name, Michelle A.; Giannini, Cosimo; Savoye, Mary; Constable, R. Todd; Sherwin, Robert S.

2014-01-01

OBJECTIVE In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation’s youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors. RESEARCH DESIGN AND METHODS Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption. RESULTS Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE). CONCLUSIONS This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D. PMID:25139883

Leptin is associated with exaggerated brain reward and emotion responses to food images in adolescent obesity.

PubMed

Jastreboff, Ania M; Lacadie, Cheryl; Seo, Dongju; Kubat, Jessica; Van Name, Michelle A; Giannini, Cosimo; Savoye, Mary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia; Sinha, Rajita

2014-11-01

In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation's youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors. Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption. Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE). This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

A face-selective ventral occipito-temporal map of the human brain with intracerebral potentials

PubMed Central

Jonas, Jacques; Jacques, Corentin; Liu-Shuang, Joan; Brissart, Hélène; Colnat-Coulbois, Sophie; Maillard, Louis; Rossion, Bruno

2016-01-01

Human neuroimaging studies have identified a network of distinct face-selective regions in the ventral occipito-temporal cortex (VOTC), with a right hemispheric dominance. To date, there is no evidence for this hemispheric and regional specialization with direct measures of brain activity. To address this gap in knowledge, we recorded local neurophysiological activity from 1,678 contact electrodes implanted in the VOTC of a large group of epileptic patients (n = 28). They were presented with natural images of objects at a rapid fixed rate (six images per second: 6 Hz), with faces interleaved as every fifth stimulus (i.e., 1.2 Hz). High signal-to-noise ratio face-selective responses were objectively (i.e., exactly at the face stimulation frequency) identified and quantified throughout the whole VOTC. Face-selective responses were widely distributed across the whole VOTC, but also spatially clustered in specific regions. Among these regions, the lateral section of the right middle fusiform gyrus showed the largest face-selective response by far, offering, to our knowledge, the first supporting evidence of two decades of neuroimaging observations with direct neural measures. In addition, three distinct regions with a high proportion of face-selective responses were disclosed in the right ventral anterior temporal lobe, a region that is undersampled in neuroimaging because of magnetic susceptibility artifacts. A high proportion of contacts responding only to faces (i.e., “face-exclusive” responses) were found in these regions, suggesting that they contain populations of neurons involved in dedicated face-processing functions. Overall, these observations provide a comprehensive mapping of visual category selectivity in the whole human VOTC with direct neural measures. PMID:27354526

Effects of Fructose vs Glucose on Regional Cerebral Blood Flow in Brain Regions Involved With Appetite and Reward Pathways

PubMed Central

Page, Kathleen A.; Chan, Owen; Arora, Jagriti; Belfort-DeAguiar, Renata; Dzuira, James; Roehmholdt, Brian; Cline, Gary W.; Naik, Sarita; Sinha, Rajita; Constable, R. Todd; Sherwin, Robert S.

2014-01-01

Importance Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety. Objective To study neurophysiological factors that might underlie associations between fructose consumption and weight gain. Design, Setting, and Participants Twenty healthy adult volunteers underwent 2 magnetic resonance imaging sessions at Yale University in conjunction with fructose or glucose drink ingestion in a blinded, random-order, crossover design. Main Outcome Measures Relative changes in hypothalamic regional cerebral blood flow (CBF) after glucose or fructose ingestion. Secondary outcomes included whole-brain analyses to explore regional CBF changes, functional connectivity analysis to investigate correlations between the hypothalamus and other brain region responses, and hormone responses to fructose and glucose ingestion. Results There was a significantly greater reduction in hypothalamic CBF after glucose vs fructose ingestion (–5.45 vs 2.84 mL/g per minute, respectively; mean difference, 8.3 mL/g per minute [95% CI of mean difference, 1.87-14.70]; P=.01). Glucose ingestion (compared with baseline) increased functional connectivity between the hypothalamus and the thalamus and striatum. Fructose increased connectivity between the hypothalamus and thalamus but not the striatum. Regional CBF within the hypothalamus, thalamus, insula, anterior cingulate, and striatum (appetite and reward regions) was reduced after glucose ingestion compared with baseline (P<.05 significance threshold, family-wise error [FWE] whole-brain corrected). In contrast, fructose reduced regional CBF in the thalamus, hippocampus, posterior cingulate cortex, fusiform, and visual cortex (P<.05 significance threshold, FWE whole-brain corrected). In whole-brain voxel-level analyses, there were no significant differences between direct comparisons of fructose vs glucose sessions following correction for multiple comparisons. Fructose vs glucose ingestion resulted in lower peak levels of serum glucose (mean difference, 41.0 mg/dL [95% CI, 27.7-54.5]; P<.001), insulin (mean difference, 49.6 μU/mL [95% CI, 38.2-61.1]; P<.001), and glucagon-like polypep-tide 1 (mean difference, 2.1 pmol/L [95% CI, 0.9-3.2]; P=.01). Conclusion and Relevance In a series of exploratory analyses, consumption of fructose compared with glucose resulted in a distinct pattern of regional CBF and a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels. PMID:23280226

Direct gaze elicits atypical activation of the theory-of-mind network in autism spectrum conditions.

PubMed

von dem Hagen, Elisabeth A H; Stoyanova, Raliza S; Rowe, James B; Baron-Cohen, Simon; Calder, Andrew J

2014-06-01

Eye contact plays a key role in social interaction and is frequently reported to be atypical in individuals with autism spectrum conditions (ASCs). Despite the importance of direct gaze, previous functional magnetic resonance imaging in ASC has generally focused on paradigms using averted gaze. The current study sought to determine the neural processing of faces displaying direct and averted gaze in 18 males with ASC and 23 matched controls. Controls showed an increased response to direct gaze in brain areas implicated in theory-of-mind and gaze perception, including medial prefrontal cortex, temporoparietal junction, posterior superior temporal sulcus region, and amygdala. In contrast, the same regions showed an increased response to averted gaze in individuals with an ASC. This difference was confirmed by a significant gaze direction × group interaction. Relative to controls, participants with ASC also showed reduced functional connectivity between these regions. We suggest that, in the typical brain, perceiving another person gazing directly at you triggers spontaneous attributions of mental states (e.g. he is "interested" in me), and that such mental state attributions to direct gaze may be reduced or absent in the autistic brain.

Adolescents growing up amidst intractable conflict attenuate brain response to pain of outgroup.

PubMed

Levy, Jonathan; Goldstein, Abraham; Influs, Moran; Masalha, Shafiq; Zagoory-Sharon, Orna; Feldman, Ruth

2016-11-29

Adolescents' participation in intergroup conflicts comprises an imminent global risk, and understanding its neural underpinnings may open new perspectives. We assessed Jewish-Israeli and Arab-Palestinian adolescents for brain response to the pain of ingroup/outgroup protagonists using magnetoencephalography (MEG), one-on-one positive and conflictual interactions with an outgroup member, attitudes toward the regional conflict, and oxytocin levels. A neural marker of ingroup bias emerged, expressed via alpha modulations in the somatosensory cortex (S1) that characterized an automatic response to the pain of all protagonists followed by rebound/enhancement to ingroup pain only. Adolescents' hostile social interactions with outgroup members and uncompromising attitudes toward the conflict influenced this neural marker. Furthermore, higher oxytocin levels in the Jewish-Israeli majority and tighter brain-to-brain synchrony among group members in the Arab-Palestinian minority enhanced the neural ingroup bias. Findings suggest that in cases of intractable intergroup conflict, top-down control mechanisms may block the brain's evolutionary-ancient resonance to outgroup pain, pinpointing adolescents' interpersonal and sociocognitive processes as potential targets for intervention.

Immediate early gene expression following exposure to acoustic and visual components of courtship in zebra finches.

PubMed

Avey, Marc T; Phillmore, Leslie S; MacDougall-Shackleton, Scott A

2005-12-07

Sensory driven immediate early gene expression (IEG) has been a key tool to explore auditory perceptual areas in the avian brain. Most work on IEG expression in songbirds such as zebra finches has focused on playback of acoustic stimuli and its effect on auditory processing areas such as caudal medial mesopallium (CMM) caudal medial nidopallium (NCM). However, in a natural setting, the courtship displays of songbirds (including zebra finches) include visual as well as acoustic components. To determine whether the visual stimulus of a courting male modifies song-induced expression of the IEG ZENK in the auditory forebrain we exposed male and female zebra finches to acoustic (song) and visual (dancing) components of courtship. Birds were played digital movies with either combined audio and video, audio only, video only, or neither audio nor video (control). We found significantly increased levels of Zenk response in the auditory region CMM in the two treatment groups exposed to acoustic stimuli compared to the control group. The video only group had an intermediate response, suggesting potential effect of visual input on activity in these auditory brain regions. Finally, we unexpectedly found a lateralization of Zenk response that was independent of sex, brain region, or treatment condition, such that Zenk immunoreactivity was consistently higher in the left hemisphere than in the right and the majority of individual birds were left-hemisphere dominant.

Experimental Traumatic Brain Injury Results in Long-Term Recovery of Functional Responsiveness in Sensory Cortex but Persisting Structural Changes and Sensorimotor, Cognitive, and Emotional Deficits.

PubMed

Johnstone, Victoria P A; Wright, David K; Wong, Kendrew; O'Brien, Terence J; Rajan, Ramesh; Shultz, Sandy R

2015-09-01

Traumatic brain injury (TBI) is a leading cause of death worldwide. In recent studies, we have shown that experimental TBI caused an immediate (24-h post) suppression of neuronal processing, especially in supragranular cortical layers. We now examine the long-term effects of experimental TBI on the sensory cortex and how these changes may contribute to a range of TBI morbidities. Adult male Sprague-Dawley rats received either a moderate lateral fluid percussion injury (n=14) or a sham surgery (n=12) and 12 weeks of recovery before behavioral assessment, magnetic resonance imaging, and electrophysiological recordings from the barrel cortex. TBI rats demonstrated sensorimotor deficits, cognitive impairments, and anxiety-like behavior, and this was associated with significant atrophy of the barrel cortex and other brain structures. Extracellular recordings from ipsilateral barrel cortex revealed normal neuronal responsiveness and diffusion tensor MRI showed increased fractional anisotropy, axial diffusivity, and tract density within this region. These findings suggest that long-term recovery of neuronal responsiveness is owing to structural reorganization within this region. Therefore, it is likely that long-term structural and functional changes within sensory cortex post-TBI may allow for recovery of neuronal responsiveness, but that this recovery does not remediate all behavioral deficits.

Visual and auditory steady-state responses in attention-deficit/hyperactivity disorder.

PubMed

Khaleghi, Ali; Zarafshan, Hadi; Mohammadi, Mohammad Reza

2018-05-22

We designed a study to investigate the patterns of the steady-state visual evoked potential (SSVEP) and auditory steady-state response (ASSR) in adolescents with attention-deficit/hyperactivity disorder (ADHD) when performing a motor response inhibition task. Thirty 12- to 18-year-old adolescents with ADHD and 30 healthy control adolescents underwent an electroencephalogram (EEG) examination during steady-state stimuli when performing a stop-signal task. Then, we calculated the amplitude and phase of the steady-state responses in both visual and auditory modalities. Results showed that adolescents with ADHD had a significantly poorer performance in the stop-signal task during both visual and auditory stimuli. The SSVEP amplitude of the ADHD group was larger than that of the healthy control group in most regions of the brain, whereas the ASSR amplitude of the ADHD group was smaller than that of the healthy control group in some brain regions (e.g., right hemisphere). In conclusion, poorer task performance (especially inattention) and neurophysiological results in ADHD demonstrate a possible impairment in the interconnection of the association cortices in the parietal and temporal lobes and the prefrontal cortex. Also, the motor control problems in ADHD may arise from neural deficits in the frontoparietal and occipitoparietal systems and other brain structures such as cerebellum.

Cerebral oxidative metabolism mapping in four genetic mouse models of anxiety and mood disorders.

PubMed

Matrov, Denis; Kaart, Tanel; Lanfumey, Laurence; Maldonado, Rafael; Sharp, Trevor; Tordera, Rosa M; Kelly, Paul A; Deakin, Bill; Harro, Jaanus

2018-06-07

The psychopathology of depression is highly complex and the outcome of studies on animal models is divergent. In order to find brain regions that could be metabolically distinctively active across a variety of mouse depression models and to compare the interconnectivity of brain regions of wild-type and such genetically modified mice, histochemical mapping of oxidative metabolism was performed by the measurement of cytochrome oxidase activity. We included mice with the heterozygous knockout of the vesicular glutamate transporter (VGLUT 1 -/+ ), full knockout of the cannabinoid 1 receptor (CB1 -/- ), an anti-sense knockdown of the glucocorticoid receptor (GRi) and overexpression of the human 5-hydroxytryptamine transporter (h5-HTT). Altogether 76 mouse brains were studied to measure oxidative metabolism in one hundred brain regions, and the obtained dataset was submitted to a variety of machine learning algorithms and multidimensional scaling. Overall, the top brain regions having the largest contribution to classification into depression model were the lateroanterior hypothalamic nucleus, the anterior part of the basomedial amygdaloid nucleus, claustrum, the suprachiasmatic nucleus, the ventromedial hypothalamic nucleus, and the anterior hypothalamic area. In terms of the patterns of inter-regional relationship between wild-type and genetically modified mice there was little overall difference, while the most deviating brain regions were cortical amygdala and ventrolateral and ventral posteromedial thalamic nuclei. The GRi mice that most clearly differed from their controls exhibited deviation of connectivity for a number of brain regions, such as ventrolateral thalamic nucleus, the intermediate part of the lateral septal nucleus, the anteriodorsal part of the medial amygdaloid nucleus, the medial division of the central amygdaloid nucleus, ventral pallidum, nucleus of the vertical limb of the diagonal band, anteroventral parts of the thalamic nucleus and parts of the bed nucleus of the stria terminalis. Conclusively, the GRi mouse model was characterized by changes in the functional connectivity of the extended amygdala and stress response circuits. Copyright © 2018 Elsevier B.V. All rights reserved.

Brain mediators of the effects of noxious heat on pain

PubMed Central

Atlas, Lauren Y.; Lindquist, Martin A.; Bolger, Niall; Wager, Tor D.

2014-01-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. While useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this paper, we used multi-level mediation analysis to identify brain mediators of pain—regions whose trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across four levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including: a) somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and b) two networks co-localized with ‘default mode’ regions in which stimulus intensity-related decreases mediated increased pain. We also identified ‘thermosensory’ regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. PMID:24845572

Elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation.

PubMed

Li, Yan; Deng, Jianxin; Zhou, Jun; Li, Xueen

2016-11-01

Corresponding to pre-puncture and post-puncture insertion, elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation are investigated, respectively. Elastic mechanical properties in pre-puncture are investigated through pre-puncture needle insertion experiments using whole porcine brains. A linear polynomial and a second order polynomial are fitted to the average insertion force in pre-puncture. The Young's modulus in pre-puncture is calculated from the slope of the two fittings. Viscoelastic mechanical properties of brain tissues in post-puncture insertion are investigated through indentation stress relaxation tests for six interested regions along a planned trajectory. A linear viscoelastic model with a Prony series approximation is fitted to the average load trace of each region using Boltzmann hereditary integral. Shear relaxation moduli of each region are calculated using the parameters of the Prony series approximation. The results show that, in pre-puncture insertion, needle force almost increases linearly with needle displacement. Both fitting lines can perfectly fit the average insertion force. The Young's moduli calculated from the slope of the two fittings are worthy of trust to model linearly or nonlinearly instantaneous elastic responses of brain tissues, respectively. In post-puncture insertion, both region and time significantly affect the viscoelastic behaviors. Six tested regions can be classified into three categories in stiffness. Shear relaxation moduli decay dramatically in short time scales but equilibrium is never truly achieved. The regional and temporal viscoelastic mechanical properties in post-puncture insertion are valuable for guiding probe insertion into each region on the implanting trajectory.

Cognitive control of drug craving inhibits brain reward regions in cocaine abusers

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

Volkow, N.D.; Fowler, J.; Wang, G.J.

Loss of control over drug taking is considered a hallmark of addiction and is critical in relapse. Dysfunction of frontal brain regions involved with inhibitory control may underlie this behavior. We evaluated whether addicted subjects when instructed to purposefully control their craving responses to drug-conditioned stimuli can inhibit limbic brain regions implicated in drug craving. We used PET and 2-deoxy-2[18F]fluoro-D-glucose to measure brain glucose metabolism (marker of brain function) in 24 cocaine abusers who watched a cocaine-cue video and compared brain activation with and without instructions to cognitively inhibit craving. A third scan was obtained at baseline (without video). Statisticalmore » parametric mapping was used for analysis and corroborated with regions of interest. The cocaine-cue video increased craving during the no-inhibition condition (pre 3 {+-} 3, post 6 {+-} 3; p < 0.001) but not when subjects were instructed to inhibit craving (pre 3 {+-} 2, post 3 {+-} 3). Comparisons with baseline showed visual activation for both cocaine-cue conditions and limbic inhibition (accumbens, orbitofrontal, insula, cingulate) when subjects purposefully inhibited craving (p < 0.001). Comparison between cocaine-cue conditions showed lower metabolism with cognitive inhibition in right orbitofrontal cortex and right accumbens (p < 0.005), which was associated with right inferior frontal activation (r = -0.62, p < 0.005). Decreases in metabolism in brain regions that process the predictive (nucleus accumbens) and motivational value (orbitofrontal cortex) of drug-conditioned stimuli were elicited by instruction to inhibit cue-induced craving. This suggests that cocaine abusers may retain some ability to inhibit craving and that strengthening fronto-accumbal regulation may be therapeutically beneficial in addiction.« less

Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk.

PubMed

Corlier, Fabian; Hafzalla, George; Faskowitz, Joshua; Kuller, Lewis H; Becker, James T; Lopez, Oscar L; Thompson, Paul M; Braskie, Meredith N

2018-05-15

Inflammatory processes may contribute to risk for Alzheimer's disease (AD) and age-related brain degeneration. Metabolic and genetic risk factors, and physical activity may, in turn, influence these inflammatory processes. Some of these risk factors are modifiable, and interact with each other. Understanding how these processes together relate to brain aging will help to inform future interventions to treat or prevent cognitive decline. We used brain magnetic resonance imaging (MRI) to scan 335 older adult humans (mean age 77.3 ± 3.4 years) who remained non-demented for the duration of the 9-year longitudinal study. We used structural equation modeling (SEM) in a subset of 226 adults to evaluate whether measures of baseline peripheral inflammation (serum C-reactive protein levels; CRP), mediated the baseline contributions of genetic and metabolic risk, and physical activity, to regional cortical thickness in AD-relevant brain regions at study year 9. We found that both baseline metabolic risk and AD risk variant apolipoprotein E ε4 (APOE4), modulated baseline serum CRP. Higher baseline CRP levels, in turn, predicted thinner regional cortex at year 9, and mediated an effect between higher metabolic risk and thinner cortex in those regions. A higher polygenic risk score composed of variants in immune-associated AD risk genes (other than APOE) was associated with thinner regional cortex. However, CRP levels did not mediate this effect, suggesting that other mechanisms may be responsible for the elevated AD risk. We found interactions between genetic and environmental factors and structural brain health. Our findings support the role of metabolic risk and peripheral inflammation in age-related brain decline. Copyright © 2018 Elsevier Inc. All rights reserved.

The role of left inferior frontal cortex during audiovisual speech perception in infants.

PubMed

Altvater-Mackensen, Nicole; Grossmann, Tobias

2016-06-01

In the first year of life, infants' speech perception attunes to their native language. While the behavioral changes associated with native language attunement are fairly well mapped, the underlying mechanisms and neural processes are still only poorly understood. Using fNIRS and eye tracking, the current study investigated 6-month-old infants' processing of audiovisual speech that contained matching or mismatching auditory and visual speech cues. Our results revealed that infants' speech-sensitive brain responses in inferior frontal brain regions were lateralized to the left hemisphere. Critically, our results further revealed that speech-sensitive left inferior frontal regions showed enhanced responses to matching when compared to mismatching audiovisual speech, and that infants with a preference to look at the speaker's mouth showed an enhanced left inferior frontal response to speech compared to infants with a preference to look at the speaker's eyes. These results suggest that left inferior frontal regions play a crucial role in associating information from different modalities during native language attunement, fostering the formation of multimodal phonological categories. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Regional Homogeneity Predicts Creative Insight: A Resting-State fMRI Study.

PubMed

Lin, Jiabao; Cui, Xuan; Dai, Xiaoying; Mo, Lei

2018-01-01

Creative insight plays an important role in our daily life. Previous studies have investigated the neural correlates of creative insight by functional magnetic resonance imaging (fMRI), however, the intrinsic resting-state brain activity associated with creative insight is still unclear. In the present study, we used regional homogeneity (ReHo) as an index in resting-state fMRI (rs-fMRI) to identify brain regions involved in individual differences in creative insight, which was compued by the response time (RT) of creative Chinese character chunk decomposition. The findings indicated that ReHo in the anterior cingulate cortex (ACC)/caudate nucleus (CN) and angular gyrus (AG)/superior temporal gyrus (STG)/inferior parietal lobe (IPL) negatively predicted creative insight. Furthermore, these findings suggested that spontaneous brain activity in multiple regions related to breaking and establishing mental sets, goal-directed solutions exploring, shifting attention, forming new associations and emotion experience contributes to creative insight. In conclusion, the present study provides new evidence to further understand the cognitive processing and neural correlates of creative insight.

Failures of Sustained Attention in Life, Lab, and Brain: Ecological Validity of the SART

ERIC Educational Resources Information Center

Smilek, Daniel; Carriere, Jonathan S. A.; Cheyne, J. Allan

2010-01-01

The Sustained Attention to Response Task (SART) is a widely used tool in cognitive neuroscience increasingly employed to identify brain regions associated with failures of sustained attention. An important claim of the SART is that it is significantly related to real-world problems of sustained attention such as those experienced by TBI and ADHD…

Structural brain aging and speech production: a surface-based brain morphometry study.

PubMed

Tremblay, Pascale; Deschamps, Isabelle

2016-07-01

While there has been a growing number of studies examining the neurofunctional correlates of speech production over the past decade, the neurostructural correlates of this immensely important human behaviour remain less well understood, despite the fact that previous studies have established links between brain structure and behaviour, including speech and language. In the present study, we thus examined, for the first time, the relationship between surface-based cortical thickness (CT) and three different behavioural indexes of sublexical speech production: response duration, reaction times and articulatory accuracy, in healthy young and older adults during the production of simple and complex meaningless sequences of syllables (e.g., /pa-pa-pa/ vs. /pa-ta-ka/). The results show that each behavioural speech measure was sensitive to the complexity of the sequences, as indicated by slower reaction times, longer response durations and decreased articulatory accuracy in both groups for the complex sequences. Older adults produced longer speech responses, particularly during the production of complex sequence. Unique age-independent and age-dependent relationships between brain structure and each of these behavioural measures were found in several cortical and subcortical regions known for their involvement in speech production, including the bilateral anterior insula, the left primary motor area, the rostral supramarginal gyrus, the right inferior frontal sulcus, the bilateral putamen and caudate, and in some region less typically associated with speech production, such as the posterior cingulate cortex.

Audio-tactile integration and the influence of musical training.

PubMed

Kuchenbuch, Anja; Paraskevopoulos, Evangelos; Herholz, Sibylle C; Pantev, Christo

2014-01-01

Perception of our environment is a multisensory experience; information from different sensory systems like the auditory, visual and tactile is constantly integrated. Complex tasks that require high temporal and spatial precision of multisensory integration put strong demands on the underlying networks but it is largely unknown how task experience shapes multisensory processing. Long-term musical training is an excellent model for brain plasticity because it shapes the human brain at functional and structural levels, affecting a network of brain areas. In the present study we used magnetoencephalography (MEG) to investigate how audio-tactile perception is integrated in the human brain and if musicians show enhancement of the corresponding activation compared to non-musicians. Using a paradigm that allowed the investigation of combined and separate auditory and tactile processing, we found a multisensory incongruency response, generated in frontal, cingulate and cerebellar regions, an auditory mismatch response generated mainly in the auditory cortex and a tactile mismatch response generated in frontal and cerebellar regions. The influence of musical training was seen in the audio-tactile as well as in the auditory condition, indicating enhanced higher-order processing in musicians, while the sources of the tactile MMN were not influenced by long-term musical training. Consistent with the predictive coding model, more basic, bottom-up sensory processing was relatively stable and less affected by expertise, whereas areas for top-down models of multisensory expectancies were modulated by training.

Perceived quality of maternal care in childhood and structure and function of mothers’ brain

PubMed Central

Kim, Pilyoung; Leckman, James F.; Mayes, Linda C.; Newman, Michal-Ann; Feldman, Ruth; Swain, James E.

2014-01-01

Animal studies indicate that early maternal care has long-term effects on brain areas related to social attachment and parenting, whereas neglectful mothering is linked with heightened stress reactivity in the hippocampus across the lifespan. The present study explores the possibility, using magnetic resonance imaging, that perceived quality of maternal care in childhood is associated with brain structure and functional responses to salient infant stimuli among human mothers in the first postpartum month. Mothers who reported higher maternal care in childhood showed larger grey matter volumes in the superior and middle frontal gyri, orbital gyrus, superior temporal gyrus and fusiform gyrus. In response to infant cries, these mothers exhibited higher activations in the middle frontal gyrus, superior temporal gyrus and fusiform gyrus, whereas mothers reporting lower maternal care showed increased hippocampal activations. These findings suggest that maternal care in childhood may be associated with anatomy and functions in brain regions implicated in appropriate responsivity to infant stimuli in human mothers. PMID:20590729

Effect of heat stress on brain 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in some vertebrate species.

PubMed

Mohamed, M I; Rahman, T A

1982-01-01

1. The variations in 5-HT and 5-HIAA levels following heat exposure and split heat doses were determined in the different brain regions of Gerbillus pyramidum, Streptopelia senegalensis aegyptiaca and Agama stellio. 2. Heat exposure was found to be associated with an increase in the levels of the two indole compounds. 3. The 5-HT concentrations increased markedly in the three species following the first heat dose and decreased following the second dose in the various brain regions except in the cerebellum of Agama. 4. The increased 5-HT levels when animals are exposed to high temperature probably represent a response to activate heat-loss mechanisms and to depress heat production.

Altruistic behavior: mapping responses in the brain

PubMed Central

Filkowski, Megan M; Cochran, R Nick; Haas, Brian W

2016-01-01

Altruism is an important social construct related to human relationships and the way many interpersonal and economic decisions are made. Recent progress in social neuroscience research shows that altruism is associated with a specific pattern of brain activity. The tendency to engage in altruistic behaviors is associated with greater activity within limbic regions such as the nucleus accumbens and anterior cingulate cortex in addition to cortical regions such as the medial prefrontal cortex and temporoparietal junction. Here, we review existing theoretical models of altruism as well as recent empirical neuroimaging research demonstrating how altruism is processed within the brain. This review not only highlights the progress in neuroscience research on altruism but also shows that there exist several open questions that remain unexplored. PMID:28580317

The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults

PubMed Central

Cortese, Bernadette M.; Uhde, Thomas W.; Brady, Kathleen T.; McClernon, F. Joseph; Yang, Qing X.; Collins, Heather R.; LeMatty, Todd; Hartwell, Karen J.

2015-01-01

Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor + picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multi-sensory, but not unisensory cues, was significantly related to participants’ level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. PMID:26475784

The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults.

PubMed

Cortese, Bernadette M; Uhde, Thomas W; Brady, Kathleen T; McClernon, F Joseph; Yang, Qing X; Collins, Heather R; LeMatty, Todd; Hartwell, Karen J

2015-12-30

Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor+picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multisensory, but not unisensory cues, was significantly related to participants' level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Brain function differences in language processing in children and adults with autism.

PubMed

Williams, Diane L; Cherkassky, Vladimir L; Mason, Robert A; Keller, Timothy A; Minshew, Nancy J; Just, Marcel Adam

2013-08-01

Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language-processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

Brain Function Differences in Language Processing in Children and Adults with Autism

PubMed Central

Williams, Diane L.; Cherkassky, Vladimir L.; Mason, Robert A.; Keller, Timothy A.; Minshew, Nancy J.; Just, Marcel Adam

2015-01-01

Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language-processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience. PMID:23495230

Brain anatomical networks in world class gymnasts: a DTI tractography study.

PubMed

Wang, Bin; Fan, Yuanyuan; Lu, Min; Li, Shumei; Song, Zheng; Peng, Xiaoling; Zhang, Ruibin; Lin, Qixiang; He, Yong; Wang, Jun; Huang, Ruiwang

2013-01-15

The excellent motor skills of world class gymnasts amaze everyone. People marvel at the way they precisely control their movements and wonder how the brain structure and function of these elite athletes differ from those of non-athletes. In this study, we acquired diffusion images from thirteen world class gymnasts and fourteen matched controls, constructed their anatomical networks, and calculated the topological properties of each network based on graph theory. From a connectivity-based analysis, we found that most of the edges with increased connection density in the champions were linked to brain regions that are located in the sensorimotor, attentional, and default-mode systems. From graph-based metrics, we detected significantly greater global and local efficiency but shorter characteristic path length in the anatomical networks of the champions compared with the controls. Moreover, in the champions we found a significantly higher nodal degree and greater regional efficiency in several brain regions that correspond to motor and attention functions. These included the left precentral gyrus, left postcentral gyrus, right anterior cingulate gyrus and temporal lobes. In addition, we revealed an increase in the mean fractional anisotropy of the corticospinal tract in the champions, possibly in response to long-term gymnastic training. Our study indicates that neuroanatomical adaptations and plastic changes occur in gymnasts' brain anatomical networks either in response to long-term intensive gymnastic training or as an innate predisposition or both. Our findings may help to explain gymnastic skills at the highest levels of performance and aid in understanding the neural mechanisms that distinguish expert gymnasts from novices. Copyright © 2012 Elsevier Inc. All rights reserved.

Remembering what could have happened: Neural correlates of episodic counterfactual thinking

PubMed Central

De Brigard, F; Addis, D.R.; Ford, J.H.; Schacter, D.L.; Giovanello, K.S

2014-01-01

Recent evidence suggests that our capacities to remember the past and to imagine what might happen in the future largely depend on the same core brain network that includes the middle temporal lobe, the posterior cingulate/retrosplenial cortex, the inferior parietal lobe, the medial prefrontal cortex, and the lateral temporal cortex. However, the extent to which regions of this core brain network are also responsible for our capacity to think about what could have happened in our past, yet did not occur (i.e., episodic counterfactual thinking), is still unknown. The present study examined this issue. Using a variation of the experimental recombination paradigm (Addis et al., 2009), participants were asked both to remember personal past events and to envision alternative outcomes to such events while undergoing functional magnetic resonance imaging. Three sets of analyses were performed on the imaging data in order to investigate two related issues. First, a mean-centered spatiotemporal partial least square (PLS) analysis identified a pattern of brain activity across regions of the core network that was common to episodic memory and episodic counterfactual thinking. Second, a non-rotated PLS analysis identified two different patterns of brain activity for likely and unlikely episodic counterfactual thoughts, with the former showing significant overlap with the set of regions engaged during episodic recollection. Finally, a parametric modulation was conducted to explore the differential engagement of brain regions during counterfactual thinking, revealing that areas such as the parahippocampal gyrus and the right hippocampus were modulated by the subjective likelihood of counterfactual simulations. These results suggest that episodic counterfactual thinking engages regions that form the core brain network, and also that the subjective likelihood of our counterfactual thoughts modulates the engagement of different areas within this set of regions. PMID:23376052

Modulation of thermal pain-related brain activity with virtual reality: evidence from fMRI.

PubMed

Hoffman, Hunter G; Richards, Todd L; Coda, Barbara; Bills, Aric R; Blough, David; Richards, Anne L; Sharar, Sam R

2004-06-07

This study investigated the neural correlates of virtual reality analgesia. Virtual reality significantly reduced subjective pain ratings (i.e. analgesia). Using fMRI, pain-related brain activity was measured for each participant during conditions of no virtual reality and during virtual reality (order randomized). As predicted, virtual reality significantly reduced pain-related brain activity in all five regions of interest; the anterior cingulate cortex, primary and secondary somatosensory cortex, insula, and thalamus (p<0.002, corrected). Results showed direct modulation of human brain pain responses by virtual reality distraction. Copyright 2004 Lippincott Williams and Wilkins

Effects of Insulin Detemir and NPH Insulin on Body Weight and Appetite-Regulating Brain Regions in Human Type 1 Diabetes: A Randomized Controlled Trial

PubMed Central

van Golen, Larissa W.; Veltman, Dick J.; IJzerman, Richard G.; Deijen, Jan Berend; Heijboer, Annemieke C.; Barkhof, Frederik; Drent, Madeleine L.; Diamant, Michaela

2014-01-01

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli. Trial Registration ClinicalTrials.gov NCT00626080. PMID:24739875

Effects of insulin detemir and NPH insulin on body weight and appetite-regulating brain regions in human type 1 diabetes: a randomized controlled trial.

PubMed

van Golen, Larissa W; Veltman, Dick J; IJzerman, Richard G; Deijen, Jan Berend; Heijboer, Annemieke C; Barkhof, Frederik; Drent, Madeleine L; Diamant, Michaela

2014-01-01

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli. ClinicalTrials.gov NCT00626080.

Blunted striatal responses to favorite-food cues in smokers.

PubMed

Jastreboff, Ania M; Sinha, Rajita; Lacadie, Cheryl M; Balodis, Iris M; Sherwin, Robert; Potenza, Marc N

2015-01-01

Although tobacco-smoking is associated with relatively leaner body mass and smoking cessation with weight gain, the brain mechanisms underlying these relationships are not well understood. Smokers compared to non-smokers have shown diminished neural responses to non-tobacco rewarding stimuli (e.g., monetary rewards), but brain responses to favorite-food cues have not been investigated relative to smoking status. We hypothesized that smokers would exhibit diminished neural responses compared to non-smokers in response to favorite-food cues in motivation-reward and emotion-regulating regions of the brain. Twenty-three smokers and 23 non-smokers matched based on body mass index (BMI), age, and gender listened to personalized favorite-food cue, stress, and neutral-relaxing audiotapes during fMRI. During favorite-food cue exposure, smokers versus non-smokers exhibited diminished activations in the caudate, putamen, insula, and thalamus. Neural responses during stress and neutral-relaxing conditions were similar across groups. Subjective food-craving ratings were similar across groups. The relatively diminished neural responses to favorite-food cues in smokers may contribute to lower BMI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Blunted Striatal Responses to Favorite Food Cues in Smokers*

PubMed Central

Jastreboff, Ania M.; Sinha, Rajita; Lacadie, Cheryl M.; Balodis, Iris M.; Sherwin, Robert; Potenza, Marc N.

2014-01-01

Background Although tobacco-smoking is associated with relatively leaner body mass and smoking cessation with weight gain, the brain mechanisms underlying these relationships are not well understood. Smokers compared to non-smokers have shown diminished neural responses to non-tobacco rewarding stimuli (e.g., monetary rewards), but brain responses to favorite-food cues have not been investigated relative to smoking status. We hypothesized that smokers would exhibit diminished neural responses compared to non-smokers in response to favorite-food cues in motivation-reward and emotion-regulating regions of the brain. Methods Twenty-three smokers and 23 non-smokers matched based on body mass index (BMI), age, and gender listened to personalized favorite-food-cue, stress, and neutral-relaxing audiotapes during fMRI. Results During favorite-food-cue exposure, smokers versus non-smokers exhibited diminished activations in the caudate, putamen, insula, and thalamus. Neural responses during stress and neutral-relaxing conditions were similar across groups. Subjective food-craving ratings were similar across groups. Conclusions The relatively diminished neural responses to favorite-food cues in smokers may contribute to lower BMI. PMID:25444233

Clarifying the Ghrelin System’s Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand

PubMed Central

Edwards, Alexander; Abizaid, Alfonso

2017-01-01

Ghrelin is a hormone predominantly produced in and secreted from the stomach. Ghrelin is involved in many physiological processes including feeding, the stress response, and in modulating learning, memory and motivational processes. Ghrelin does this by binding to its receptor, the growth hormone secretagogue receptor (GHSR), a receptor found in relatively high concentrations in hypothalamic and mesolimbic brain regions. While the feeding and metabolic effects of ghrelin can be explained by the effects of this hormone on regions of the brain that have a more permeable blood brain barrier (BBB), ghrelin produced within the periphery demonstrates a limited ability to reach extrahypothalamic regions where GHSRs are expressed. Therefore, one of the most pressing unanswered questions plaguing ghrelin research is how GHSRs, distributed in brain regions protected by the BBB, are activated despite ghrelin’s predominant peripheral production and poor ability to transverse the BBB. This manuscript will describe how peripheral ghrelin activates central GHSRs to encourage feeding, and how central ghrelin synthesis and ghrelin independent activation of GHSRs may also contribute to the modulation of feeding behaviours. PMID:28422060

Differential recruitment of theory of mind brain network across three tasks: An independent component analysis.

PubMed

Thye, Melissa D; Ammons, Carla J; Murdaugh, Donna L; Kana, Rajesh K

2018-07-16

Social neuroscience research has focused on an identified network of brain regions primarily associated with processing Theory of Mind (ToM). However, ToM is a broad cognitive process, which encompasses several sub-processes, such as mental state detection and intentional attribution, and the connectivity of brain regions underlying the broader ToM network in response to paradigms assessing these sub-processes requires further characterization. Standard fMRI analyses which focus only on brain activity cannot capture information about ToM processing at a network level. An alternative method, independent component analysis (ICA), is a data-driven technique used to isolate intrinsic connectivity networks, and this approach provides insight into network-level regional recruitment. In this fMRI study, three complementary, but distinct ToM tasks assessing mental state detection (e.g. RMIE: Reading the Mind in the Eyes; RMIV: Reading the Mind in the Voice) and intentional attribution (Causality task) were each analyzed using ICA in order to separately characterize the recruitment and functional connectivity of core nodes in the ToM network in response to the sub-processes of ToM. Based on visual comparison of the derived networks for each task, the spatiotemporal network patterns were similar between the RMIE and RMIV tasks, which elicited mentalizing about the mental states of others, and these networks differed from the network derived for the Causality task, which elicited mentalizing about goal-directed actions. The medial prefrontal cortex, precuneus, and right inferior frontal gyrus were seen in the components with the highest correlation with the task condition for each of the tasks highlighting the role of these regions in general ToM processing. Using a data-driven approach, the current study captured the differences in task-related brain response to ToM in three distinct ToM paradigms. The findings of this study further elucidate the neural mechanisms associated with mental state detection and causal attribution, which represent possible sub-processes of the complex construct of ToM processing. Published by Elsevier B.V.

Predicting Individual Differences in Placebo Analgesia: Contributions of Brain Activity during Anticipation and Pain Experience

PubMed Central

Wager, Tor D.; Atlas, Lauren Y.; Leotti, Lauren A.; Rilling, James K.

2012-01-01

Recent studies have identified brain correlates of placebo analgesia, but none have assessed how accurately patterns of brain activity can predict individual differences in placebo responses. We reanalyzed data from two fMRI studies of placebo analgesia (N = 47), using patterns of fMRI activity during the anticipation and experience of pain to predict new subjects’ scores on placebo analgesia and placebo-induced changes in pain processing. We used a cross-validated regression procedure, LASSO-PCR, which provided both unbiased estimates of predictive accuracy and interpretable maps of which regions are most important for prediction. Increased anticipatory activity in a frontoparietal network and decreases in a posterior insular/temporal network predicted placebo analgesia. Patterns of anticipatory activity across the cortex predicted a moderate amount of variance in the placebo response (~12% overall, ~40% for study 2 alone), which is substantial considering the multiple likely contributing factors. The most predictive regions were those associated with emotional appraisal, rather than cognitive control or pain processing. During pain, decreases in limbic and paralimbic regions most strongly predicted placebo analgesia. Responses within canonical pain-processing regions explained significant variance in placebo analgesia, but the pattern of effects was inconsistent with widespread decreases in nociceptive processing. Together, the findings suggest that engagement of emotional appraisal circuits drives individual variation in placebo analgesia, rather than early suppression of nociceptive processing. This approach provides a framework that will allow prediction accuracy to increase as new studies provide more precise information for future predictive models. PMID:21228154

New developments in brain research of internet and gaming disorder.

PubMed

Weinstein, Aviv; Livny, Abigail; Weizman, Abraham

2017-04-01

There is evidence that the neural mechanisms underlying Internet Gaming Disorder (IGD) resemble those of drug addiction. Functional Magnetic Resonance Imaging (fMRI) studies of the resting state and measures of gray matter volume have shown that Internet game playing was associated with changes to brain regions responsible for attention and control, impulse control, motor function, emotional regulation, sensory-motor coordination. Furthermore, Internet game playing was associated with lower white matter density in brain regions that are involved in decision-making, behavioral inhibition and emotional regulation. Videogame playing involved changes in reward inhibitory mechanisms and loss of control. Structural brain imaging studies showed alterations in the volume of the ventral striatum that is an important part of the brain's reward mechanisms. Finally, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and lower dopamine transporter and dopamine receptor D 2 occupancy indicating sub-sensitivity of dopamine reward mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain

PubMed Central

Venkat, Poornima; Chopp, Michael; Chen, Jieli

2016-01-01

The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases. PMID:27374823

New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain.

PubMed

Venkat, Poornima; Chopp, Michael; Chen, Jieli

2016-06-30

The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases.

Reward-related brain response and craving correlates of marijuana cue exposure: a preliminary study in treatment-seeking marijuana-dependent subjects.

PubMed

Goldman, Marina; Szucs-Reed, Regina P; Jagannathan, Kanchana; Ehrman, Ronald N; Wang, Ze; Li, Yin; Suh, Jesse J; Kampman, Kyle; O'Brien, Charles P; Childress, Anna Rose; Franklin, Teresa R

2013-01-01

: Determining the brain substrates underlying the motivation to abuse addictive drugs is critical for understanding and treating addictive disorders. Laboratory neuroimaging studies have demonstrated differential activation of limbic and motivational circuitry (eg, amygdala, hippocampus, ventral striatum, insula, and orbitofrontal cortex) triggered by cocaine, heroin, nicotine, and alcohol cues. The literature on neural responses to marijuana cues is sparse. Thus, the goals of this study were to characterize the brain's response to marijuana cues, a major motivator underlying drug use and relapse, and determine whether these responses are linked to self-reported craving in a clinically relevant population of treatment-seeking marijuana-dependent subjects. : Marijuana craving was assessed in 12 marijuana-dependent subjects using the Marijuana Craving Questionnaire-Short Form. Subsequently, blood oxygen level dependent functional magnetic resonance imaging data were acquired during exposure to alternating 20-second blocks of marijuana-related versus matched nondrug visual cues. : Brain activation during marijuana cue exposure was significantly greater in the bilateral amygdala and the hippocampus. Significant positive correlations between craving scores and brain activation were found in the ventral striatum and the medial and lateral orbitofrontal cortex (P < 0.0001). : This study presents direct evidence for a link between reward-relevant brain responses to marijuana cues and craving and extends the current literature on marijuana cue reactivity. Furthermore, the correlative relationship between craving and brain activity in reward-related regions was observed in a clinically relevant sample (treatment-seeking marijuana-dependent subjects). Results are consistent with prior findings in cocaine, heroin, nicotine, and alcohol cue studies, indicating that the brain substrates of cue-triggered drug motivation are shared across abused substances.

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection

PubMed Central

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments. PMID:28928987

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection.

PubMed

Phillips, Cristy

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments.

Human-like brain hemispheric dominance in birdsong learning.

PubMed

Moorman, Sanne; Gobes, Sharon M H; Kuijpers, Maaike; Kerkhofs, Amber; Zandbergen, Matthijs A; Bolhuis, Johan J

2012-07-31

Unlike nonhuman primates, songbirds learn to vocalize very much like human infants acquire spoken language. In humans, Broca's area in the frontal lobe and Wernicke's area in the temporal lobe are crucially involved in speech production and perception, respectively. Songbirds have analogous brain regions that show a similar neural dissociation between vocal production and auditory perception and memory. In both humans and songbirds, there is evidence for lateralization of neural responsiveness in these brain regions. Human infants already show left-sided dominance in their brain activation when exposed to speech. Moreover, a memory-specific left-sided dominance in Wernicke's area for speech perception has been demonstrated in 2.5-mo-old babies. It is possible that auditory-vocal learning is associated with hemispheric dominance and that this association arose in songbirds and humans through convergent evolution. Therefore, we investigated whether there is similar song memory-related lateralization in the songbird brain. We exposed male zebra finches to tutor or unfamiliar song. We found left-sided dominance of neuronal activation in a Broca-like brain region (HVC, a letter-based name) of juvenile and adult zebra finch males, independent of the song stimulus presented. In addition, juvenile males showed left-sided dominance for tutor song but not for unfamiliar song in a Wernicke-like brain region (the caudomedial nidopallium). Thus, left-sided dominance in the caudomedial nidopallium was specific for the song-learning phase and was memory-related. These findings demonstrate a remarkable neural parallel between birdsong and human spoken language, and they have important consequences for our understanding of the evolution of auditory-vocal learning and its neural mechanisms.

From Vivaldi to Beatles and back: predicting lateralized brain responses to music.

PubMed

Alluri, Vinoo; Toiviainen, Petri; Lund, Torben E; Wallentin, Mikkel; Vuust, Peter; Nandi, Asoke K; Ristaniemi, Tapani; Brattico, Elvira

2013-12-01

We aimed at predicting the temporal evolution of brain activity in naturalistic music listening conditions using a combination of neuroimaging and acoustic feature extraction. Participants were scanned using functional Magnetic Resonance Imaging (fMRI) while listening to two musical medleys, including pieces from various genres with and without lyrics. Regression models were built to predict voxel-wise brain activations which were then tested in a cross-validation setting in order to evaluate the robustness of the hence created models across stimuli. To further assess the generalizability of the models we extended the cross-validation procedure by including another dataset, which comprised continuous fMRI responses of musically trained participants to an Argentinean tango. Individual models for the two musical medleys revealed that activations in several areas in the brain belonging to the auditory, limbic, and motor regions could be predicted. Notably, activations in the medial orbitofrontal region and the anterior cingulate cortex, relevant for self-referential appraisal and aesthetic judgments, could be predicted successfully. Cross-validation across musical stimuli and participant pools helped identify a region of the right superior temporal gyrus, encompassing the planum polare and the Heschl's gyrus, as the core structure that processed complex acoustic features of musical pieces from various genres, with or without lyrics. Models based on purely instrumental music were able to predict activation in the bilateral auditory cortices, parietal, somatosensory, and left hemispheric primary and supplementary motor areas. The presence of lyrics on the other hand weakened the prediction of activations in the left superior temporal gyrus. Our results suggest spontaneous emotion-related processing during naturalistic listening to music and provide supportive evidence for the hemispheric specialization for categorical sounds with realistic stimuli. We herewith introduce a powerful means to predict brain responses to music, speech, or soundscapes across a large variety of contexts. © 2013.

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol

PubMed Central

Sawant, Onkar B.; Ramadoss, Jayanth; Hankins, Gary D.; Wu, Guoyao

2014-01-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75–2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid–base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid–base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy. PMID:24810329

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol.

PubMed

Sawant, Onkar B; Ramadoss, Jayanth; Hankins, Gary D; Wu, Guoyao; Washburn, Shannon E

2014-08-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75-2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid-base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid-base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy.

Behavioral Analysis of Genetically Modified Mice Indicates Essential Roles of Neurosteroidal Estrogen

PubMed Central

Honda, Shin-Ichiro; Wakatsuki, Toru; Harada, Nobuhiro

2011-01-01

Aromatase in the mouse brain is expressed only in the nerve cells of specific brain regions with a transient peak during the neonatal period when sexual behaviors become organized. The aromatase-knockout (ArKO) mouse, generated to shed light on the physiological functions of estrogen in the brain, exhibited various abnormal behaviors, concomitant with undetectable estrogen and increased androgen in the blood. To further elucidate the effects of neurosteroidal estrogens on behavioral phenotypes, we first prepared an brain-specific aromatase transgenic (bsArTG) mouse by introduction of a human aromatase transgene controlled under a −6.5 kb upstream region of the brain-specific promoter of the mouse aromatase gene into fertilized mouse eggs, because the −6.5 kb promoter region was previously shown to contain the minimal essential element responsible for brain-specific spatiotemporal expression. Then, an ArKO mouse expressing the human aromatase only in the brain was generated by crossing the bsArTG mouse with the ArKO mouse. The resulting mice (ArKO/bsArTG mice) nearly recovered from abnormal sexual, aggressive, and locomotive (exploratory) behaviors, in spite of having almost the same serum levels of estrogen and androgen as the adult ArKO mouse. These results suggest that estrogens locally synthesized in the specific neurons of the perinatal mouse brain directly act on the neurons and play crucial roles in the organization of neuronal networks participating in the control of sexual, aggressive, and locomotive (exploratory) behaviors. PMID:22654807

Abnormal brain synchrony in Down Syndrome☆

PubMed Central

Anderson, Jeffrey S.; Nielsen, Jared A.; Ferguson, Michael A.; Burback, Melissa C.; Cox, Elizabeth T.; Dai, Li; Gerig, Guido; Edgin, Jamie O.; Korenberg, Julie R.

2013-01-01

Down Syndrome is the most common genetic cause for intellectual disability, yet the pathophysiology of cognitive impairment in Down Syndrome is unknown. We compared fMRI scans of 15 individuals with Down Syndrome to 14 typically developing control subjects while they viewed 50 min of cartoon video clips. There was widespread increased synchrony between brain regions, with only a small subset of strong, distant connections showing underconnectivity in Down Syndrome. Brain regions showing negative correlations were less anticorrelated and were among the most strongly affected connections in the brain. Increased correlation was observed between all of the distributed brain networks studied, with the strongest internetwork correlation in subjects with the lowest performance IQ. A functional parcellation of the brain showed simplified network structure in Down Syndrome organized by local connectivity. Despite increased interregional synchrony, intersubject correlation to the cartoon stimuli was lower in Down Syndrome, indicating that increased synchrony had a temporal pattern that was not in response to environmental stimuli, but idiosyncratic to each Down Syndrome subject. Short-range, increased synchrony was not observed in a comparison sample of 447 autism vs. 517 control subjects from the Autism Brain Imaging Exchange (ABIDE) collection of resting state fMRI data, and increased internetwork synchrony was only observed between the default mode and attentional networks in autism. These findings suggest immature development of connectivity in Down Syndrome with impaired ability to integrate information from distant brain regions into coherent distributed networks. PMID:24179822

The Causal Inference of Cortical Neural Networks during Music Improvisations

PubMed Central

Wan, Xiaogeng; Crüts, Björn; Jensen, Henrik Jeldtoft

2014-01-01

We present an EEG study of two music improvisation experiments. Professional musicians with high level of improvisation skills were asked to perform music either according to notes (composed music) or in improvisation. Each piece of music was performed in two different modes: strict mode and “let-go” mode. Synchronized EEG data was measured from both musicians and listeners. We used one of the most reliable causality measures: conditional Mutual Information from Mixed Embedding (MIME), to analyze directed correlations between different EEG channels, which was combined with network theory to construct both intra-brain and cross-brain networks. Differences were identified in intra-brain neural networks between composed music and improvisation and between strict mode and “let-go” mode. Particular brain regions such as frontal, parietal and temporal regions were found to play a key role in differentiating the brain activities between different playing conditions. By comparing the level of degree centralities in intra-brain neural networks, we found a difference between the response of musicians and the listeners when comparing the different playing conditions. PMID:25489852

The causal inference of cortical neural networks during music improvisations.

PubMed

Wan, Xiaogeng; Crüts, Björn; Jensen, Henrik Jeldtoft

2014-01-01

We present an EEG study of two music improvisation experiments. Professional musicians with high level of improvisation skills were asked to perform music either according to notes (composed music) or in improvisation. Each piece of music was performed in two different modes: strict mode and "let-go" mode. Synchronized EEG data was measured from both musicians and listeners. We used one of the most reliable causality measures: conditional Mutual Information from Mixed Embedding (MIME), to analyze directed correlations between different EEG channels, which was combined with network theory to construct both intra-brain and cross-brain networks. Differences were identified in intra-brain neural networks between composed music and improvisation and between strict mode and "let-go" mode. Particular brain regions such as frontal, parietal and temporal regions were found to play a key role in differentiating the brain activities between different playing conditions. By comparing the level of degree centralities in intra-brain neural networks, we found a difference between the response of musicians and the listeners when comparing the different playing conditions.

Activation of nuclear transcription factor-kappaB in mouse brain induced by a simulated microgravity environment

NASA Technical Reports Server (NTRS)

Wise, Kimberly C.; Manna, Sunil K.; Yamauchi, Keiko; Ramesh, Vani; Wilson, Bobby L.; Thomas, Renard L.; Sarkar, Shubhashish; Kulkarni, Anil D.; Pellis, Neil R.; Ramesh, Govindarajan T.

2005-01-01

Microgravity induces inflammatory responses and modulates immune functions that may increase oxidative stress. Exposure to a microgravity environment induces adverse neurological effects; however, there is little research exploring the etiology of these effects resulting from exposure to such an environment. It is also known that spaceflight is associated with increase in oxidative stress; however, this phenomenon has not been reproduced in land-based simulated microgravity models. In this study, an attempt has been made to show the induction of reactive oxygen species (ROS) in mice brain, using ground-based microgravity simulator. Increased ROS was observed in brain stem and frontal cortex with concomitant decrease in glutathione, on exposing mice to simulated microgravity for 7 d. Oxidative stress-induced activation of nuclear factor-kappaB was observed in all the regions of the brain. Moreover, mitogen-activated protein kinase kinase was phosphorylated equally in all regions of the brain exposed to simulated microgravity. These results suggest that exposure of brain to simulated microgravity can induce expression of certain transcription factors, and these have been earlier argued to be oxidative stress dependent.

Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z

PubMed Central

Badgaiyan, Rajendra D.; Thanos, Panayotis K.; Kulkarni, Praveen; Giordano, John; Baron, David; Gold, Mark S.

2017-01-01

Dopaminergic reward dysfunction in addictive behaviors is well supported in the literature. There is evidence that alterations in synchronous neural activity between brain regions subserving reward and various cognitive functions may significantly contribute to substance-related disorders. This study presents the first evidence showing that a pro-dopaminergic nutraceutical (KB220Z) significantly enhances, above placebo, functional connectivity between reward and cognitive brain areas in the rat. These include the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, prelimbic and infralimbic loci. Significant functional connectivity, increased brain connectivity volume recruitment (potentially neuroplasticity), and dopaminergic functionality were found across the brain reward circuitry. Increases in functional connectivity were specific to these regions and were not broadly distributed across the brain. While these initial findings have been observed in drug naïve rodents, this robust, yet selective response implies clinical relevance for addicted individuals at risk for relapse, who show reductions in functional connectivity after protracted withdrawal. Future studies will evaluate KB220Z in animal models of addiction. PMID:28445527

Regional homogeneity, resting-state functional connectivity and amplitude of low frequency fluctuation associated with creativity measured by divergent thinking in a sex-specific manner.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Yokoyama, Ryoichi; Kotozaki, Yuka; Nakagawa, Seishu; Sekiguchi, Atsushi; Iizuka, Kunio; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Makoto Miyauchi, Carlos; Shinada, Takamitsu; Sakaki, Kohei; Nozawa, Takayuki; Ikeda, Shigeyuki; Yokota, Susumu; Daniele, Magistro; Sassa, Yuko; Kawashima, Ryuta

2017-05-15

Brain connectivity is traditionally thought to be important for creativity. Here we investigated the associations of creativity measured by divergent thinking (CMDT) with resting-state functional magnetic imaging (fMRI) measures and their sex differences. We examined these relationships in the brains of 1277 healthy young adults. Whole-brain analyses revealed a significant interaction between verbal CMDT and sex on (a) regional homogeneity within an area from the left anterior temporal lobe (b) on the resting state functional connectivity (RSFC) between the mPFC and the left inferior frontal gyrus and (c) on fractional amplitude of low frequency fluctuations (fALFF) in several distinct areas, including the precuneus and middle cingulate gyrus, left middle temporal gyrus, right middle frontal gyrus, and cerebellum. These interactions were mediated by positive correlations in females and negative correlations in males. These findings suggest that greater CMDT in females is reflected by (a) regional coherence (regional homogeneity) of brain areas responsible for representing and combining concepts as well as (b) the efficient functional connection (RSFC) between the key areas for the default state of cognitive activity and speech production, and (c) greater spontaneous neural activity (fALFF) during the resting of brain areas involved in frontal lobe functions, default cognitive activities, and language functions. Furthermore, these findings suggest that the associations between creativity and resting state brain connectivity patterns are different between males and females. Copyright © 2017 Elsevier Inc. All rights reserved.

Hyperconnectivity is a fundamental response to neurological disruption.

PubMed

Hillary, Frank G; Roman, Cristina A; Venkatesan, Umesh; Rajtmajer, Sarah M; Bajo, Ricardo; Castellanos, Nazareth D

2015-01-01

In the cognitive and clinical neurosciences, the past decade has been marked by dramatic growth in a literature examining brain "connectivity" using noninvasive methods. We offer a critical review of the blood oxygen level dependent functional MRI (BOLD fMRI) literature examining neural connectivity changes in neurological disorders with focus on brain injury and dementia. The goal is to demonstrate that there are identifiable shifts in local and large-scale network connectivity that can be predicted by the degree of pathology. We anticipate that the most common network response to neurological insult is hyperconnectivity but that this response depends upon demand and resource availability. To examine this hypothesis, we initially reviewed the results from 1,426 studies examining functional brain connectivity in individuals diagnosed with multiple sclerosis, traumatic brain injury, mild cognitive impairment, and Alzheimer's disease. Based upon inclusionary criteria, 126 studies were included for detailed analysis. RESULTS from 126 studies examining local and whole brain connectivity demonstrated increased connectivity in traumatic brain injury and multiple sclerosis. This finding is juxtaposed with findings in mild cognitive impairment and Alzheimer's disease where there is a shift to diminished connectivity as degeneration progresses. This summary of the functional imaging literature using fMRI methods reveals that hyperconnectivity is a common response to neurological disruption and that it may be differentially observable across brain regions. We discuss the factors contributing to both hyper- and hypoconnectivity results after neurological disruption and the implications these findings have for network plasticity. PsycINFO Database Record (c) 2015 APA, all rights reserved.

In vivo imaging and analysis of cerebrovascular hemodynamic responses and tissue oxygenation in the mouse brain.

PubMed

Kisler, Kassandra; Lazic, Divna; Sweeney, Melanie D; Plunkett, Shane; El Khatib, Mirna; Vinogradov, Sergei A; Boas, David A; Sakadži, Sava; Zlokovic, Berislav V

2018-06-01

Cerebrovascular dysfunction has an important role in the pathogenesis of multiple brain disorders. Measurement of hemodynamic responses in vivo can be challenging, particularly as techniques are often not described in sufficient detail and vary between laboratories. We present a set of standardized in vivo protocols that describe high-resolution two-photon microscopy and intrinsic optical signal (IOS) imaging to evaluate capillary and arteriolar responses to a stimulus, regional hemodynamic responses, and oxygen delivery to the brain. The protocol also describes how to measure intrinsic NADH fluorescence to understand how blood O 2 supply meets the metabolic demands of activated brain tissue, and to perform resting-state absolute oxygen partial pressure (pO 2 ) measurements of brain tissue. These methods can detect cerebrovascular changes at far higher resolution than MRI techniques, although the optical nature of these techniques limits their achievable imaging depths. Each individual procedure requires 1-2 h to complete, with two to three procedures typically performed per animal at a time. These protocols are broadly applicable in studies of cerebrovascular function in healthy and diseased brain in any of the existing mouse models of neurological and vascular disorders. All these procedures can be accomplished by a competent graduate student or experienced technician, except the two-photon measurement of absolute pO 2 level, which is better suited to a more experienced, postdoctoral-level researcher.

A temporary local energy pool coupled to neuronal activity: fluctuations of extracellular lactate levels in rat brain monitored with rapid-response enzyme-based sensor.

PubMed

Hu, Y; Wilson, G S

1997-10-01

A successfully developed enzyme-based lactate microsensor with rapid response time allows the direct and continuous in vivo measurement of lactic acid concentration with high temporal resolution in brain extracellular fluid. The fluctuations coupled to neuronal activity in extracellular lactate concentration were explored in the dentate gyrus of the hippocampus of the rat brain after electrical stimulation of the perforant pathway. Extracellular glucose and oxygen levels were also detected simultaneously by coimplantation of a fast-response glucose sensor and an oxygen electrode, to provide novel information of trafficking of energy substances in real time related to local neuronal activity. The results first give a comprehensive picture of complementary energy supply and use of lactate and glucose in the intact brain tissue. In response to acute neuronal activation, the brain tissue shifts immediately to significant energy supply by lactate. A local temporary fuel "reservoir" is established behind the blood-brain barrier, evidenced by increased extracellular lactate concentration. The pool can be depleted rapidly, up to 28% in 10-12 s, by massive, acute neuronal use after stimulation and can be replenished in approximately 20 s. Glutamate-stimulated astrocytic glycolysis and the increase of regional blood flow may regulate the lactate concentration of the pool in different time scales to maintain local energy homeostasis.

An fMRI study of emotional face processing in adolescent major depression.

PubMed

Hall, Leah M J; Klimes-Dougan, Bonnie; Hunt, Ruskin H; Thomas, Kathleen M; Houri, Alaa; Noack, Emily; Mueller, Bryon A; Lim, Kelvin O; Cullen, Kathryn R

2014-10-01

Major depressive disorder (MDD) often begins during adolescence when the brain is still maturing. To better understand the neurobiological underpinnings of MDD early in development, this study examined brain function in response to emotional faces in adolescents with MDD and healthy (HC) adolescents using functional magnetic resonance imaging (fMRI). Thirty-two unmedicated adolescents with MDD and 23 healthy age- and gender-matched controls completed an fMRI task viewing happy and fearful faces. Fronto-limbic regions of interest (ROI; bilateral amygdala, insula, subgenual and rostral anterior cingulate cortices) and whole-brain analyses were conducted to examine between-group differences in brain function. ROI analyses revealed that patients had greater bilateral amygdala activity than HC in response to viewing fearful versus happy faces, which remained significant when controlling for comorbid anxiety. Whole-brain analyses revealed that adolescents with MDD had lower activation compared to HC in a right hemisphere cluster comprised of the insula, superior/middle temporal gyrus, and Heschl׳s gyrus when viewing fearful faces. Brain activity in the subgenual anterior cingulate cortex was inversely correlated with depression severity. Limitations include a cross-sectional design with a modest sample size and use of a limited range of emotional stimuli. Results replicate previous studies that suggest emotion processing in adolescent MDD is associated with abnormalities within fronto-limbic brain regions. Findings implicate elevated amygdalar arousal to negative stimuli in adolescents with depression and provide new evidence for a deficit in functioning of the saliency network, which may be a future target for early intervention and MDD treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Multisensory stimuli elicit altered oscillatory brain responses at gamma frequencies in patients with schizophrenia

PubMed Central

Stone, David B.; Coffman, Brian A.; Bustillo, Juan R.; Aine, Cheryl J.; Stephen, Julia M.

2014-01-01

Deficits in auditory and visual unisensory responses are well documented in patients with schizophrenia; however, potential abnormalities elicited from multisensory audio-visual stimuli are less understood. Further, schizophrenia patients have shown abnormal patterns in task-related and task-independent oscillatory brain activity, particularly in the gamma frequency band. We examined oscillatory responses to basic unisensory and multisensory stimuli in schizophrenia patients (N = 46) and healthy controls (N = 57) using magnetoencephalography (MEG). Time-frequency decomposition was performed to determine regions of significant changes in gamma band power by group in response to unisensory and multisensory stimuli relative to baseline levels. Results showed significant behavioral differences between groups in response to unisensory and multisensory stimuli. In addition, time-frequency analysis revealed significant decreases and increases in gamma-band power in schizophrenia patients relative to healthy controls, which emerged both early and late over both sensory and frontal regions in response to unisensory and multisensory stimuli. Unisensory gamma-band power predicted multisensory gamma-band power differently by group. Furthermore, gamma-band power in these regions predicted performance in select measures of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) test battery differently by group. These results reveal a unique pattern of task-related gamma-band power in schizophrenia patients relative to controls that may indicate reduced inhibition in combination with impaired oscillatory mechanisms in patients with schizophrenia. PMID:25414652

Dissociable meta-analytic brain networks contribute to coordinated emotional processing.

PubMed

Riedel, Michael C; Yanes, Julio A; Ray, Kimberly L; Eickhoff, Simon B; Fox, Peter T; Sutherland, Matthew T; Laird, Angela R

2018-06-01

Meta-analytic techniques for mining the neuroimaging literature continue to exert an impact on our conceptualization of functional brain networks contributing to human emotion and cognition. Traditional theories regarding the neurobiological substrates contributing to affective processing are shifting from regional- towards more network-based heuristic frameworks. To elucidate differential brain network involvement linked to distinct aspects of emotion processing, we applied an emergent meta-analytic clustering approach to the extensive body of affective neuroimaging results archived in the BrainMap database. Specifically, we performed hierarchical clustering on the modeled activation maps from 1,747 experiments in the affective processing domain, resulting in five meta-analytic groupings of experiments demonstrating whole-brain recruitment. Behavioral inference analyses conducted for each of these groupings suggested dissociable networks supporting: (1) visual perception within primary and associative visual cortices, (2) auditory perception within primary auditory cortices, (3) attention to emotionally salient information within insular, anterior cingulate, and subcortical regions, (4) appraisal and prediction of emotional events within medial prefrontal and posterior cingulate cortices, and (5) induction of emotional responses within amygdala and fusiform gyri. These meta-analytic outcomes are consistent with a contemporary psychological model of affective processing in which emotionally salient information from perceived stimuli are integrated with previous experiences to engender a subjective affective response. This study highlights the utility of using emergent meta-analytic methods to inform and extend psychological theories and suggests that emotions are manifest as the eventual consequence of interactions between large-scale brain networks. © 2018 Wiley Periodicals, Inc.

Enhanced Brain Responses to Pain-Related Words in Chronic Back Pain Patients and Their Modulation by Current Pain.

PubMed

Ritter, Alexander; Franz, Marcel; Puta, Christian; Dietrich, Caroline; Miltner, Wolfgang H R; Weiss, Thomas

2016-08-10

Previous functional magnetic resonance imaging (fMRI) studies in healthy controls (HC) and pain-free migraine patients found activations to pain-related words in brain regions known to be activated while subjects experience pain. The aim of the present study was to identify neural activations induced by pain-related words in a sample of chronic back pain (CBP) patients experiencing current chronic pain compared to HC. In particular, we were interested in how current pain influences brain activations induced by pain-related adjectives. Subjects viewed pain-related, negative, positive, and neutral words; subjects were asked to generate mental images related to these words during fMRI scanning. Brain activation was compared between CBP patients and HC in response to the different word categories and examined in relation to current pain in CBP patients. Pain-related words vs. neutral words activated a network of brain regions including cingulate cortex and insula in subjects and patients. There was stronger activation in medial and dorsolateral prefrontal cortex (DLPFC) and anterior midcingulate cortex in CPB patients than in HC. The magnitude of activation for pain-related vs. negative words showed a negative linear relationship to CBP patients' current pain. Our findings confirm earlier observations showing that pain-related words activate brain networks similar to noxious stimulation. Importantly, CBP patients show even stronger activation of these structures while merely processing pain-related words. Current pain directly influences on this activation.

Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli.

PubMed

Hasen, Nina S; Gammie, Stephen C

2011-03-01

The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female. Copyright © 2010 Elsevier B.V. All rights reserved.

Growth of melanoma brain tumors monitored by photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

2010-07-01

Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

An autoradiographic analysis of cholinergic receptors in mouse brain after chronic nicotine treatment

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

Pauly, J.R.; Marks, M.J.; Gross, S.D.

1991-09-01

Quantitative autoradiographic procedures were used to examine the effects of chronic nicotine infusion on the number of central nervous system nicotinic cholinergic receptors. Female DBA mice were implanted with jugular cannulas and infused with saline or various doses of nicotine (0.25, 0.5, 1.0 or 2.0 mg/kg/hr) for 10 days. The animals were then sacrificed and the brains were removed and frozen in isopentane. Cryostat sections were collected and prepared for autoradiographic procedures as previously described. Nicotinic cholinergic receptors were labeled with L-(3H)nicotine or alpha-(125I)bungarotoxin; (3H)quinuclidinyl benzilate was used to measure muscarinic cholinergic receptor binding. Chronic nicotine infusion increased the numbermore » of sites labeled by (3H)nicotine in most brain areas. However, the extent of the increase in binding as well as the dose-response curves for the increase were widely different among brain regions. After the highest treatment dose, binding was increased in 67 of 86 regions measured. Septal and thalamic regions were most resistant to change. Nicotinic binding measured by alpha-(125I)bungarotoxin also increased after chronic treatment, but in a less robust fashion. At the highest treatment dose, only 26 of 80 regions were significantly changes. Muscarinic binding was not altered after chronic nicotine treatment. These data suggest that brain regions are not equivalent in the mechanisms that regulate alterations in nicotinic cholinergic receptor binding after chronic nicotine treatment.« less

Functional magnetic resonance imaging can be used to explore tactile and nociceptive processing in the infant brain

PubMed Central

Williams, Gemma; Fabrizi, Lorenzo; Meek, Judith; Jackson, Deborah; Tracey, Irene; Robertson, Nicola; Slater, Rebeccah; Fitzgerald, Maria

2015-01-01

Aim Despite the importance of neonatal skin stimulation, little is known about activation of the newborn human infant brain by sensory stimulation of the skin. We carried out functional magnetic resonance imaging (fMRI) to assess the feasibility of measuring brain activation to a range of mechanical stimuli applied to the skin of neonatal infants. Methods We studied 19 term infants with a mean age of 13 days. Brain activation was measured in response to brushing, von Frey hair (vFh) punctate stimulation and, in one case, nontissue damaging pinprick stimulation of the plantar surface of the foot. Initial whole brain analysis was followed by region of interest analysis of specific brain areas. Results Distinct patterns of functional brain activation were evoked by brush and vFh punctate stimulation, which were reduced, but still present, under chloral hydrate sedation. Brain activation increased with increasing stimulus intensity. The feasibility of using pinprick stimulation in fMRI studies was established in one unsedated healthy full-term infant. Conclusion Distinct brain activity patterns can be measured in response to different modalities and intensities of skin sensory stimulation in term infants. This indicates the potential for fMRI studies in exploring tactile and nociceptive processing in the infant brain. PMID:25358870

Brain Responses Underlying Anthropomorphism, Agency, and Social Attribution in Autism Spectrum Disorder

PubMed Central

Ammons, Carla J.; Doss, Constance F.; Bala, David; Kana, Rajesh K.

2018-01-01

Background: Theory of Mind (ToM), the ability to attribute mental states to oneself and others, is frequently impaired in Autism Spectrum Disorder (ASD) and may result from altered activation of social brain regions. Conversely, Typically Developing (TD) individuals overextend ToM and show a strong tendency to anthropomorphize and interpret biological motion in the environment. Less is known about how the degree of anthropomorphism influences intentional attribution and engagement of the social brain in ASD. Objective: This fMRI study examines the extent of anthropomorphism, its role in social attribution, and the underlying neural responses in ASD and TD using a series of human stick figures and geometrical shapes. Methods: 14 ASD and 14 TD adults watched videos of stick figures and triangles interacting in random or socially meaningful ways while in an fMRI scanner. In addition, they completed out-of-scanner measures of ToM skill and real-world social deficits. Whole brain statistical analysis was performed for regression and within and between group comparisons of all conditions using SPM12’s implementation of the general linear model. Results: ToM network regions were activated in response to social movement and human-like characters in ASD and TD. In addition, greater ToM ability was associated with increased TPJ and MPFC activity while watching stick figures; whereas more severe social symptoms were associated with reduced right TPJ activation in response to social movement. Conclusion: These results suggest that degree of anthropomorphism does not differentially affect social attribution in ASD and highlights the importance of TPJ in ToM and social attribution. PMID:29682095

Low-Fat Diet With Caloric Restriction Reduces White Matter Microglia Activation During Aging.

PubMed

Yin, Zhuoran; Raj, Divya D; Schaafsma, Wandert; van der Heijden, Roel A; Kooistra, Susanne M; Reijne, Aaffien C; Zhang, Xiaoming; Moser, Jill; Brouwer, Nieske; Heeringa, Peter; Yi, Chun-Xia; van Dijk, Gertjan; Laman, Jon D; Boddeke, Erik W G M; Eggen, Bart J L

2018-01-01

Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, and hypothalamus. Microglia, the resident macrophages of the central nervous system, are important for brain development, neural support, and homeostasis. However, the effects of diet and lifestyle on microglia during aging are only partly understood. Here, we report alterations in microglia phenotype and functions in different brain regions of mice on a high-fat diet (HFD) or low-fat diet (LFD) during aging and in response to voluntary running wheel exercise. We compared the expression levels of genes involved in immune response, phagocytosis, and metabolism in the hypothalamus of 6-month-old HFD and LFD mice. We also compared the immune response of microglia from HFD or LFD mice to peripheral inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS). Finally, we investigated the effect of diet, physical exercise, and caloric restriction (40% reduction compared to ad libitum intake) on microglia in 24-month-old HFD and LFD mice. Changes in diet caused morphological changes in microglia, but did not change the microglia response to LPS-induced systemic inflammation. Expression of phagocytic markers (i.e., Mac-2/Lgals3, Dectin-1/Clec7a, and CD16/CD32) in the white matter microglia of 24-month-old brain was markedly decreased in calorically restricted LFD mice. In conclusion, LFD resulted in reduced activation of microglia, which might be an underlying mechanism for the protective role of caloric restriction during aging-associated decline.

Functional network architecture predicts psychologically mediated analgesia related to treatment in chronic knee pain patients.

PubMed

Hashmi, Javeria Ali; Kong, Jian; Spaeth, Rosa; Khan, Sheraz; Kaptchuk, Ted J; Gollub, Randy L

2014-03-12

Placebo analgesia is an indicator of how efficiently the brain translates psychological signals conveyed by a treatment procedure into pain relief. It has been demonstrated that functional connectivity between distributed brain regions predicts placebo analgesia in chronic back pain patients. Greater network efficiency in baseline brain networks may allow better information transfer and facilitate adaptive physiological responses to psychological aspects of treatment. Here, we theorized that topological network alignments in resting state scans predict psychologically conditioned analgesic responses to acupuncture treatment in chronic knee osteoarthritis pain patients (n = 45). Analgesia was induced by building positive expectations toward acupuncture treatment with verbal suggestion and heat pain conditioning on a test site of the arm. This procedure induced significantly more analgesia after sham or real acupuncture on the test site than in a control site. The psychologically conditioned analgesia was invariant to sham versus real treatment. Efficiency of information transfer within local networks calculated with graph-theoretic measures (local efficiency and clustering coefficients) significantly predicted conditioned analgesia. Clustering coefficients in regions associated with memory, motivation, and pain modulation were closely involved in predicting analgesia. Moreover, women showed higher clustering coefficients and marginally greater pain reduction than men. Overall, analgesic response to placebo cues can be predicted from a priori resting state data by observing local network topology. Such low-cost synchronizations may represent preparatory resources that facilitate subsequent performance of brain circuits in responding to adaptive environmental cues. This suggests a potential utility of network measures in predicting placebo response for clinical use.

Brain Responses Underlying Anthropomorphism, Agency, and Social Attribution in Autism Spectrum Disorder.

PubMed

Ammons, Carla J; Doss, Constance F; Bala, David; Kana, Rajesh K

2018-01-01

Theory of Mind (ToM), the ability to attribute mental states to oneself and others, is frequently impaired in Autism Spectrum Disorder (ASD) and may result from altered activation of social brain regions. Conversely, Typically Developing (TD) individuals overextend ToM and show a strong tendency to anthropomorphize and interpret biological motion in the environment. Less is known about how the degree of anthropomorphism influences intentional attribution and engagement of the social brain in ASD. This fMRI study examines the extent of anthropomorphism, its role in social attribution, and the underlying neural responses in ASD and TD using a series of human stick figures and geometrical shapes. 14 ASD and 14 TD adults watched videos of stick figures and triangles interacting in random or socially meaningful ways while in an fMRI scanner. In addition, they completed out-of-scanner measures of ToM skill and real-world social deficits. Whole brain statistical analysis was performed for regression and within and between group comparisons of all conditions using SPM12's implementation of the general linear model. ToM network regions were activated in response to social movement and human-like characters in ASD and TD. In addition, greater ToM ability was associated with increased TPJ and MPFC activity while watching stick figures; whereas more severe social symptoms were associated with reduced right TPJ activation in response to social movement. These results suggest that degree of anthropomorphism does not differentially affect social attribution in ASD and highlights the importance of TPJ in ToM and social attribution.

Food portion size and energy density evoke different patterns of brain activation in children12

PubMed Central

Fearnbach, S Nicole; Wilson, Stephen J; Fisher, Jennifer O; Savage, Jennifer S; Rolls, Barbara J; Keller, Kathleen L

2017-01-01

Background: Large portions of food promote intake, but the mechanisms that drive this effect are unclear. Previous neuroimaging studies have identified the brain-reward and decision-making systems that are involved in the response to the energy density (ED) (kilocalories per gram) of foods, but few studies have examined the brain response to the food portion size (PS). Objective: We used functional MRI (fMRI) to determine the brain response to food images that differed in PSs (large and small) and ED (high and low). Design: Block-design fMRI was used to assess the blood oxygen level–dependent (BOLD) response to images in 36 children (7–10 y old; girls: 50%), which was tested after a 2-h fast. Pre-fMRI fullness and liking were rated on visual analog scales. A whole-brain cluster-corrected analysis was used to compare BOLD activation for main effects of the PS, ED, and their interaction. Secondary analyses were used to associate BOLD contrast values with appetitive traits and laboratory intake from meals for which the portions of all foods were increased. Results: Compared with small-PS cues, large-PS cues were associated with decreased activation in the inferior frontal gyrus (P < 0.01). Compared with low-ED cues, high-ED cues were associated with increased activation in multiple regions (e.g., in the caudate, cingulate, and precentral gyrus) and decreased activation in the insula and superior temporal gyrus (P < 0.01 for all). A PS × ED interaction was shown in the superior temporal gyrus (P < 0.01). BOLD contrast values for high-ED cues compared with low-ED cues in the insula, declive, and precentral gyrus were negatively related to appetitive traits (P < 0.05). There were no associations between the brain response to the PS and either appetitive traits or intake. Conclusions: Cues regarding food PS may be processed in the lateral prefrontal cortex, which is a region that is implicated in cognitive control, whereas ED activates multiple areas involved in sensory and reward processing. Possible implications include the development of interventions that target decision-making and reward systems differently to moderate overeating. PMID:27881393

Angular default mode network connectivity across working memory load.

PubMed

Vatansever, D; Manktelow, A E; Sahakian, B J; Menon, D K; Stamatakis, E A

2017-01-01

Initially identified during no-task, baseline conditions, it has now been suggested that the default mode network (DMN) engages during a variety of working memory paradigms through its flexible interactions with other large-scale brain networks. Nevertheless, its contribution to whole-brain connectivity dynamics across increasing working memory load has not been explicitly assessed. The aim of our study was to determine which DMN hubs relate to working memory task performance during an fMRI-based n-back paradigm with parametric increases in difficulty. Using a voxel-wise metric, termed the intrinsic connectivity contrast (ICC), we found that the bilateral angular gyri (core DMN hubs) displayed the greatest change in global connectivity across three levels of n-back task load. Subsequent seed-based functional connectivity analysis revealed that the angular DMN regions robustly interact with other large-scale brain networks, suggesting a potential involvement in the global integration of information. Further support for this hypothesis comes from the significant correlations we found between angular gyri connectivity and reaction times to correct responses. The implication from our study is that the DMN is actively involved during the n-back task and thus plays an important role related to working memory, with its core angular regions contributing to the changes in global brain connectivity in response to increasing environmental demands. Hum Brain Mapp 38:41-52, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Neural signatures of third-party punishment: evidence from penetrating traumatic brain injury.

PubMed

Glass, Leila; Moody, Lara; Grafman, Jordan; Krueger, Frank

2016-02-01

The ability to survive within a cooperative society depends on impartial third-party punishment (TPP) of social norm violations. Two cognitive mechanisms have been postulated as necessary for the successful completion of TPP: evaluation of legal responsibility and selection of a suitable punishment given the magnitude of the crime. Converging neuroimaging research suggests two supporting domain-general networks; a mentalizing network for evaluation of legal responsibility and a central-executive network for determination of punishment. A whole-brain voxel-based lesion-symptom mapping approach was used in conjunction with a rank-order TPP task to identify brain regions necessary for TPP in a large sample of patients with penetrating traumatic brain injury. Patients who demonstrated atypical TPP had specific lesions in core regions of the mentalizing (dorsomedial prefrontal cortex [PFC], ventromedial PFC) and central-executive (bilateral dorsolateral PFC, right intraparietal sulcus) networks. Altruism and executive functioning (concept formation skills) were significant predictors of TPP: altruism was uniquely associated with TPP in patients with lesions in right dorsolateral PFC and executive functioning was uniquely associated with TPP in individuals with lesions in left PFC. Our findings contribute to the extant literature to support underlying neural networks associated with TPP, with specific brain-behavior causal relationships confirming recent functional neuroimaging research. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders

PubMed Central

2012-01-01

Background Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD. We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Result Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex–MTG–IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. Conclusions These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD. PMID:22889284

Cholinesterase inhibition modulates visual and attentional brain responses in Alzheimer's disease and health.

PubMed

Bentley, Paul; Driver, Jon; Dolan, Ray J

2008-02-01

Visuo-attentional deficits occur early in Alzheimer's disease (AD) and are considered more responsive to pro-cholinergic therapy than characteristic memory disturbances. We hypothesised that neural responses in AD during visuo-attentional processing would be impaired relative to controls, yet partially susceptible to improvement with the cholinesterase inhibitor physostigmine. We studied 16 mild AD patients and 17 age-matched healthy controls, using fMRI-scanning to enable within-subject placebo-controlled comparisons of effects of physostigmine on stimulus- and attention- related brain activations, plus between-group comparisons for these. Subjects viewed face or building stimuli while performing a shallow judgement (colour of image) or a deep judgement (young/old age of depicted face or building). Behaviourally, AD subjects performed slower than controls in both tasks, while physostigmine benefited the patients for the more demanding age-judgement task. Stimulus-selective (face minus building, and vice versa) BOLD signals in precuneus and posterior parahippocampal cortex were attenuated in patients relative to controls, but increased following physostigmine. By contrast, face-selective responses in fusiform cortex were not impaired in AD and showed decreases following physostigmine for both groups. Task-dependent responses in right parietal and prefrontal cortices were diminished in AD but improved following physostigmine. A similar pattern of group and treatment effects was observed in two extrastriate cortical regions that showed physostigmine-induced enhancement of stimulus-selectivity for the deep versus shallow task. Finally, for the healthy group, physostigmine decreased stimulus and task-dependent effects, partly due to an exaggeration of selectivity during the shallow relative to deep task. The differences in brain activations between groups and treatments were not attributable merely to performance (reaction time) differences. Our results demonstrate that physostigmine can improve both stimulus- and attention-dependent responses in functionally affected extrastriate and frontoparietal regions in AD, while perturbing the normal pattern of responses in many of the same regions in healthy controls.

Cortical organization of inhibition-related functions and modulation by psychopathology

PubMed Central

Warren, Stacie L.; Crocker, Laura D.; Spielberg, Jeffery M.; Engels, Anna S.; Banich, Marie T.; Sutton, Bradley P.; Miller, Gregory A.; Heller, Wendy

2013-01-01

Individual differences in inhibition-related functions have been implicated as risk factors for a broad range of psychopathology, including anxiety and depression. Delineating neural mechanisms of distinct inhibition-related functions may clarify their role in the development and maintenance of psychopathology. The present study tested the hypothesis that activity in common and distinct brain regions would be associated with an ecologically sensitive, self-report measure of inhibition and a laboratory performance measure of prepotent response inhibition. Results indicated that sub-regions of DLPFC distinguished measures of inhibition, whereas left inferior frontal gyrus and bilateral inferior parietal cortex were associated with both types of inhibition. Additionally, co-occurring anxiety and depression modulated neural activity in select brain regions associated with response inhibition. Results imply that specific combinations of anxiety and depression dimensions are associated with failure to implement top-down attentional control as reflected in inefficient recruitment of posterior DLPFC and increased activation in regions associated with threat (MTG) and worry (BA10). Present findings elucidate possible neural mechanisms of interference that could help explain executive control deficits in psychopathology. PMID:23781192

Cortical organization of inhibition-related functions and modulation by psychopathology.

PubMed

Warren, Stacie L; Crocker, Laura D; Spielberg, Jeffery M; Engels, Anna S; Banich, Marie T; Sutton, Bradley P; Miller, Gregory A; Heller, Wendy

2013-01-01

Individual differences in inhibition-related functions have been implicated as risk factors for a broad range of psychopathology, including anxiety and depression. Delineating neural mechanisms of distinct inhibition-related functions may clarify their role in the development and maintenance of psychopathology. The present study tested the hypothesis that activity in common and distinct brain regions would be associated with an ecologically sensitive, self-report measure of inhibition and a laboratory performance measure of prepotent response inhibition. Results indicated that sub-regions of DLPFC distinguished measures of inhibition, whereas left inferior frontal gyrus and bilateral inferior parietal cortex were associated with both types of inhibition. Additionally, co-occurring anxiety and depression modulated neural activity in select brain regions associated with response inhibition. Results imply that specific combinations of anxiety and depression dimensions are associated with failure to implement top-down attentional control as reflected in inefficient recruitment of posterior DLPFC and increased activation in regions associated with threat (MTG) and worry (BA10). Present findings elucidate possible neural mechanisms of interference that could help explain executive control deficits in psychopathology.

Predicting Treatment Response in Social Anxiety Disorder From Functional Magnetic Resonance Imaging

PubMed Central

Doehrmann, Oliver; Ghosh, Satrajit S.; Polli, Frida E.; Reynolds, Gretchen O.; Horn, Franziska; Keshavan, Anisha; Triantafyllou, Christina; Saygin, Zeynep M.; Whitfield-Gabrieli, Susan; Hofmann, Stefan G.; Pollack, Mark; Gabrieli, John D.

2013-01-01

Context Current behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). To our knowledge, this is the first study to examine neuroimaging-based treatment prediction in SAD. Objective To measure brain activation in patients with SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT). Design Functional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli. Setting Patients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at Massachusetts Institute of Technology. Patients Thirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of SAD. Interventions Brain responses to angry vs neutral faces or emotional vs neutral scenes were examined with fMRI prior to initiation of CBT. Main Outcome Measures Whole-brain regression analyses with differential fMRI responses for angry vs neutral faces and changes in Liebowitz Social Anxiety Scale score as the treatment outcome measure. Results Pretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than 40% of the variance in treatment response and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline. Conclusions The results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions and more generally suggest that such biomarkers may offer evidence-based, personalized medicine approaches for optimally selecting among treatment options for a patient. PMID:22945462

Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain

PubMed Central

Lee, Won Hee; Sonntag, William E.; Mitschelen, Matthew; Yan, Han; Lee, Yong Woo

2010-01-01

Purpose Pro-inflammatory environments in the brain have been implicated in the onset and progression of neurological disorders. In the present study, we investigate the hypothesis that brain irradiation induces regionally specific alterations in cytokine gene and protein expression. Materials and methods Four month old F344 × BN rats received either whole brain irradiation with a single dose of 10 Gy γ-rays or sham-irradiation, and were maintained for 4, 8, and 24 h following irradiation. The mRNA and protein expression levels of pro-inflammatory mediators were analysed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. To elucidate the molecular mechanisms of irradiation-induced brain inflammation, effects of irradiation on the DNA-binding activity of pro-inflammatory transcription factors were also examined. Results A significant and marked up-regulation of mRNA and protein expression of pro-inflammatory mediators, including tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1), was observed in hippocampal and cortical regions isolated from irradiated brain. Cytokine expression was regionally specific since TNF-α levels were significantly elevated in cortex compared to hippocampus (57% greater) and IL-1β levels were elevated in hippocampus compared to cortical samples (126% greater). Increases in cytokine levels also were observed after irradiation of mouse BV-2 microglial cells. A series of electrophoretic mobility shift assays (EMSA) demonstrated that irradiation significantly increased activation of activator protein-1 (AP-1), nuclear factor-κB (NF-κB), and cAMP response element-binding protein (CREB). Conclusion The present study demonstrated that whole brain irradiation induces regionally specific pro-inflammatory environments through activation of AP-1, NF-κB, and CREB and overexpression of TNF-α, IL-1β, and MCP-1 in rat brain and may contribute to unique pathways for the radiation-induced impairments in tissue function. PMID:20148699

Decisions during Negatively-Framed Messages Yield Smaller Risk-Aversion-Related Brain Activation in Substance-Dependent Individuals

PubMed Central

Fukunaga, Rena; Bogg, Tim; Finn, Peter R.; Brown, Joshua W.

2012-01-01

A sizable segment of addiction research investigates the effects of persuasive message appeals on risky and deleterious behaviors. However, to date, little research has examined how various forms of message framing and corresponding behavioral choices might by mediated by risk-related brain regions. Using event-related functional magnetic resonance imaging, we investigated brain regions hypothesized to mediate the influence of message appeals on decision making in substance-dependent (SD) compared to non-substance-dependent (non-SD) individuals. The Iowa Gambling Task (IGT) was modified to include positively-framed, negatively-framed, and control messages about long-term deck payoffs. In the positively-framed condition, the SD and non-SD groups showed improved decision-making performance that corresponded to higher risk-aversion-related brain activity in the anterior cingulate cortex (ACC) and anterior insula (AI). In contrast, in the negatively-framed condition, the SD group showed poorer performance that corresponded to lower risk-aversion-related brain activity in the AI region. In addition, only the non-SD group showed a positive association between decision quality and greater risk-related activity in the ACC, regardless of message type. The findings suggest substance-dependent individuals may have reduced neurocognitive sensitivity in the ACC and AI regions involved in risk perception and aversion during decision-making, especially in response to framed messages that emphasize reduced prospects for long-term gains. PMID:23148798

Categorical encoding of color in the brain.

PubMed

Bird, Chris M; Berens, Samuel C; Horner, Aidan J; Franklin, Anna

2014-03-25

The areas of the brain that encode color categorically have not yet been reliably identified. Here, we used functional MRI adaptation to identify neuronal populations that represent color categories irrespective of metric differences in color. Two colors were successively presented within a block of trials. The two colors were either from the same or different categories (e.g., "blue 1 and blue 2" or "blue 1 and green 1"), and the size of the hue difference was varied. Participants performed a target detection task unrelated to the difference in color. In the middle frontal gyrus of both hemispheres and to a lesser extent, the cerebellum, blood-oxygen level-dependent response was greater for colors from different categories relative to colors from the same category. Importantly, activation in these regions was not modulated by the size of the hue difference, suggesting that neurons in these regions represent color categorically, regardless of metric color difference. Representational similarity analyses, which investigated the similarity of the pattern of activity across local groups of voxels, identified other regions of the brain (including the visual cortex), which responded to metric but not categorical color differences. Therefore, categorical and metric hue differences appear to be coded in qualitatively different ways and in different brain regions. These findings have implications for the long-standing debate on the origin and nature of color categories, and also further our understanding of how color is processed by the brain.

Relative vascular permeability and vascularity across different regions of the rat nasal mucosa: implications for nasal physiology and drug delivery

PubMed Central

Kumar, Niyanta N.; Gautam, Mohan; Lochhead, Jeffrey J.; Wolak, Daniel J.; Ithapu, Vamsi; Singh, Vikas; Thorne, Robert G.

2016-01-01

Intranasal administration provides a non-invasive drug delivery route that has been proposed to target macromolecules either to the brain via direct extracellular cranial nerve-associated pathways or to the periphery via absorption into the systemic circulation. Delivering drugs to nasal regions that have lower vascular density and/or permeability may allow more drug to access the extracellular cranial nerve-associated pathways and therefore favor delivery to the brain. However, relative vascular permeabilities of the different nasal mucosal sites have not yet been reported. Here, we determined that the relative capillary permeability to hydrophilic macromolecule tracers is significantly greater in nasal respiratory regions than in olfactory regions. Mean capillary density in the nasal mucosa was also approximately 5-fold higher in nasal respiratory regions than in olfactory regions. Applying capillary pore theory and normalization to our permeability data yielded mean pore diameter estimates ranging from 13–17 nm for the nasal respiratory vasculature compared to <10 nm for the vasculature in olfactory regions. The results suggest lymphatic drainage for CNS immune responses may be favored in olfactory regions due to relatively lower clearance to the bloodstream. Lower blood clearance may also provide a reason to target the olfactory area for drug delivery to the brain. PMID:27558973

Brain mediators of the effects of noxious heat on pain.

PubMed

Atlas, Lauren Y; Lindquist, Martin A; Bolger, Niall; Wager, Tor D

2014-08-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. Although useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this study, we used multi-level mediation analysis to identify brain mediators of pain--regions in which trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across 4 levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including the following: somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and 2 networks co-localized with "default mode" regions in which stimulus intensity-related decreases mediated increased pain. We also identified "thermosensory" regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Delineation of separate brain regions used for scientific versus engineering modes of thinking

NASA Astrophysics Data System (ADS)

Patterson, Clair C.

1994-08-01

Powerful, latent abilities for extreme sophistication in abstract rationalization as potential biological adaptive behavioral responses were installed entirely through accident and inadvertence by biological evolution in the Homo sapiens sapiens species of brain. These potentials were never used, either in precursor species as factors in evolutionary increase in hominid brain mass, nor in less sophisticated forms within social environments characterized by Hss tribal brain population densities. Those latent abilities for unnatural biological adaptive behavior were forced to become manifest in various ways by growths in sophistication of communication interactions engendered by large growths in brain population densities brought on by developments in agriculture at the onset of the Holocene. It is proposed that differences probably exist between regions of the Hss brain involved in utilitarian, engineering types of problem conceptualization-solving versus regions of the brain involved in nonutilitarian, artistic-scientific types of problem conceptualization-solving. Populations isolated on separate continents from diffusive contact and influence on cultural developments, and selected for comparison of developments during equivalent stages of technological and social sophistication in matching 4000 year periods, show, at the ends of those periods, marked differences in aesthetic attributes expressed in cosmogonies, music, and writing (nonutilitarian thinking related to science and art). On the other hand the two cultures show virtually identical developments in three major stages of metallurgical technologies (utilitarian thinking related to engineering). Such archaeological data suggest that utilitarian modes of thought may utilize combinations of neuronal circuits in brain regions that are conserved among tribal populations territorially separated from each other for tens of thousands of years. Such conservation may not be true for neuronal circuits involved in nonutilitarian modes of thought. It is postulated that neuronal circuits involved in nonutilitarian modes of thought are located in specific regions of the brain that are divergent features between populations that have been territorially separated for tens of thousands of years. Anatomical PET and NMRI studies of brains of modern descendants of these cultures are proposed that would seek to define these inferred differences through proper protocols of stimulation devised by those investigators.

Sex differences in directional brain responses to infant hunger cries.

PubMed

De Pisapia, Nicola; Bornstein, Marc H; Rigo, Paola; Esposito, Gianluca; De Falco, Simona; Venuti, Paola

2013-02-13

Infant cries are a critical survival mechanism that draw the attention of adult caregivers, who can then satisfy the basic needs of otherwise helpless infants. Here, we used functional neuroimaging to determine the effects of infant hunger cries on the brain activity of adults who were in a cognitively nondemanding mental state of awake rest. We found that the brains of men and women, independent of parental status (parent or nonparent), reacted differently to infant cries. Specifically, the dorsal medial prefrontal and posterior cingulate areas, known to be involved in mind wandering (the stream of thought typical of awake rest), remained active in men during exposure to infant cries, whereas in women, activity in these regions decreased. These results show sex-dependent modulation of brain responses to infant requests to be fed, and specifically, they indicate that women interrupt mind wandering when exposed to the sounds of infant hunger cries, whereas men carry on without interruption.

Cortical Activation in Response to Pure Taste Stimuli During the Physiological States of Hunger and Satiety

PubMed Central

Haase, Lori; Cerf-Ducastel, Barbara; Murphy, Claire

2009-01-01

This event-related functional magnetic resonance imaging (er-fMRI) study investigated BOLD signal change in response to a series of pure gustatory stimuli that varied in stimulus quality when subjects were hungry and sated with a nutritional preload. Group analyses showed significant differences in activation in the hunger minus satiety condition in response to sucrose, caffeine, saccharin, and citric acid within the thalamus, hippocampus, and parahippocampus. When examining the hunger and satiety conditions, activation varied as a function of stimulus, with the majority of the stimuli exhibiting significantly greater activation in the hunger state within the insula, thalamus, and substantia nigra, in contrast to decreased activation in the satiated state within the parahippocampus, hippocampus, amygdala, and anterior cingulate. Region of interest (ROI) analysis revealed two significant interactions, ROI by physiology and ROI by physiology by stimulus. In the satiety condition, the primary (inferior and superior insulae) and secondary (OFC 11 and OFC 47) taste regions exhibited significantly greater brain activation in response to all stimuli than regions involved in processing eating behavior (hypothalamus), affect (amygdala), and memory (hippocampus, parahippocampus and entorhinal cortex). These same regions demonstrated significantly greater activation within the hunger condition than the satiety condition, with the exception of the superior insula. Furthermore, the patterns of activation differed as a function taste stimulus, with greater activation in response to sucrose than to the other stimuli. These differential patterns of activation suggest that the physiological states of hunger and satiety produce divergent activation in multiple brain areas in response to different pure gustatory stimuli. PMID:19007893

Cortical activation in response to pure taste stimuli during the physiological states of hunger and satiety.

PubMed

Haase, Lori; Cerf-Ducastel, Barbara; Murphy, Claire

2009-02-01

This event-related functional magnetic resonance imaging (er-fMRI) study investigated BOLD signal change in response to a series of pure gustatory stimuli that varied in stimulus quality when subjects were hungry and sated with a nutritional pre-load. Group analyses showed significant differences in activation in the hunger minus satiety condition in response to sucrose, caffeine, saccharin, and citric acid within the thalamus, hippocampus, and parahippocampus. When examining the hunger and satiety conditions, activation varied as a function of stimulus, with the majority of the stimuli exhibiting significantly greater activation in the hunger state within the insula, thalamus, and substantia nigra, in contrast to decreased activation in the satiated state within the parahippocampus, hippocampus, amygdala, and anterior cingulate. Region of interest (ROI) analysis revealed two significant interactions, ROI by physiology and ROI by physiology by stimulus. In the satiety condition, the primary (inferior and superior insulae) and secondary (OFC 11 and OFC 47) taste regions exhibited significantly greater brain activation in response to all stimuli than regions involved in processing eating behavior (hypothalamus), affect (amygdala), and memory (hippocampus, parahippocampus and entorhinal cortex). These same regions demonstrated significantly greater activation within the hunger condition than the satiety condition, with the exception of the superior insula. Furthermore, the patterns of activation differed as a function taste stimulus, with greater activation in response to sucrose than to the other stimuli. These differential patterns of activation suggest that the physiological states of hunger and satiety produce divergent activation in multiple brain areas in response to different pure gustatory stimuli.

Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure.

PubMed

Baud, Maxime O; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J; Petit, Jean-Marie

2016-10-01

Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs cognitive functions. Intriguingly, sleep fragmentation, despite normal total sleep duration, has a similar cognitive impact, and in this paper we ask the question of whether it may also impair brain energy metabolism. To this end, we used a recently developed mouse model of 2 weeks of sleep fragmentation and measured 2-deoxy-glucose uptake and glycogen, glucose and lactate concentration in different brain regions. In order to homogenize mice behaviour during metabolic measurements, we exposed them to a novel environment for 1 h. Using an intra-hippocampal electrode, we first showed that hippocampal electroencephalograph (EEG) response to exploration was unaltered by 1 or 14 days of sleep fragmentation. However, after 14 days, sleep fragmented mice exhibited a lower uptake of 2-deoxy-glucose in cortex and hippocampus and lower cortical lactate levels than control mice. Our results suggest that long-term sleep fragmentation impaired brain metabolism to a similar extent as total sleep deprivation without affecting the neuronal responsiveness of hippocampus to a novel environment. © 2016 European Sleep Research Society.

Brain connectivity study of joint attention using frequency-domain optical imaging technique

NASA Astrophysics Data System (ADS)

Chaudhary, Ujwal; Zhu, Banghe; Godavarty, Anuradha

2010-02-01

Autism is a socio-communication brain development disorder. It is marked by degeneration in the ability to respond to joint attention skill task, from as early as 12 to 18 months of age. This trait is used to distinguish autistic from nonautistic populations. In this study, diffuse optical imaging is being used to study brain connectivity for the first time in response to joint attention experience in normal adults. The prefrontal region of the brain was non-invasively imaged using a frequency-domain based optical imager. The imaging studies were performed on 11 normal right-handed adults and optical measurements were acquired in response to joint-attention based video clips. While the intensity-based optical data provides information about the hemodynamic response of the underlying neural process, the time-dependent phase-based optical data has the potential to explicate the directional information on the activation of the brain. Thus brain connectivity studies are performed by computing covariance/correlations between spatial units using this frequency-domain based optical measurements. The preliminary results indicate that the extent of synchrony and directional variation in the pattern of activation varies in the left and right frontal cortex. The results have significant implication for research in neural pathways associated with autism that can be mapped using diffuse optical imaging tools in the future.

Aging reduces the stimulating effect of blue light on cognitive brain functions.

PubMed

Daneault, Véronique; Hébert, Marc; Albouy, Geneviève; Doyon, Julien; Dumont, Marie; Carrier, Julie; Vandewalle, Gilles

2014-01-01

Light exposure, particularly blue light, is being recognized as a potent mean to stimulate alertness and cognition in young individuals. Aging is associated with changes in alertness regulation and cognition. Whether the effect of light on cognitive brain function changes with aging is unknown, however. Cross-sectional study. Functional Neuroimaging Unit, University of Montreal Geriatric Institute. Sixteen younger (23 ± 4.1 y) and 14 older (61 ± 4.5 y) healthy participants were recruited in the current study. Blue light administration. We used functional magnetic resonance imaging to record brain responses to an auditory working memory task in young and older healthy individuals, alternatively maintained in darkness or exposed to blue light. Results show that the older brain remains capable of showing sustained responses to light in several brain areas. However, compared to young individuals, the effect of blue light is decreased in the pulvinar, amygdala, and tegmentum as well as in the insular, prefrontal, and occipital cortices in elderly individuals. The effect of blue light on brain responses diminishes with aging in areas typically involved in visual functions and in key regions for alertness regulation and higher executive processes. Our findings provide the first indications that the effect of light on cognition may be reduced in healthy aging.

Age-related differences in memory-encoding fMRI responses after accounting for decline in vascular reactivity

PubMed Central

Liu, Peiying; Hebrank, Andrew C.; Rodrigue, Karen M.; Kennedy, Kristen M.; Section, Jarren; Park, Denise C.; Lu, Hanzhang

2013-01-01

BOLD fMRI has provided a wealth of information about the aging brain. A common finding is that posterior regions of the brain manifest an age-related decrease in activation while the anterior regions show an age-related increase. Several neurocognitive models have been proposed to interpret these findings. However, one issue that has not been sufficiently considered to date is that the BOLD signal is based on vascular responses secondary to neural activity. Thus the above findings could be in part due to a vascular change, especially in view of the expected decline of vascular health with age. In the present study, we aim to examine age-related differences in memory-encoding fMRI response in the context of vascular aging. One hundred and thirty healthy subjects ranging from 20 to 89 years old underwent a scene-viewing fMRI task and, in the same session, cerebrovascular reactivity (CVR) was measured in each subject using a CO2-inhalation task. Without accounting for the influence of vascular changes, the task-activated fMRI signal showed the typical age-related decrease in visual cortex and medial temporal lobe (MTL), but manifested an increase in the right inferior frontal gyrus (IFG). In the same individuals, an age-related CVR reduction was observed in all of these regions. We then used a previously proposed normalization approach to calculate a CVR-corrected fMRI signal, which was defined as the uncorrected signal divided by CVR. Based on the CVR-corrected fMRI signal, an age-related increase is now seen in both the left and right side of IFG; and no brain regions showed a signal decrease with age. We additionally used a model-based approach to examine the fMRI data in the context of CVR, which again suggested an age-related change in the two frontal regions, but not in the visual and MTL regions. PMID:23624491

The problem with value

PubMed Central

O’Doherty, John P.

2015-01-01

Neural correlates of value have been extensively reported in a diverse set of brain regions. However, in many cases it is difficult to determine whether a particular neural response pattern corresponds to a value-signal per se as opposed to an array of alternative non-value related processes, such as outcome-identity coding, informational coding, encoding of autonomic and skeletomotor consequences, alongside previously described “salience” or “attentional” effects. Here, I review a number of experimental manipulations that can be used to test for value, and I identify the challenges in ascertaining whether a particular neural response is or is not a value signal. Finally, I emphasize that some non-value related signals may be especially informative as a means of providing insight into the nature of the decision-making related computations that are being implemented in a particular brain region. PMID:24726573

Gender differences in brain activity generated by unpleasant word stimuli concerning body image: an fMRI study.

PubMed

Shirao, Naoko; Okamoto, Yasumasa; Mantani, Tomoyuki; Okamoto, Yuri; Yamawaki, Shigeto

2005-01-01

We have previously reported that the temporomesial area, including the amygdala, is activated in women when processing unpleasant words concerning body image. To detect gender differences in brain activation during processing of these words. Functional magnetic resonance imaging was used to investigate 13 men and 13 women during an emotional decision task consisting of unpleasant words concerning body image and neutral words. The left medial prefrontal cortex and hippocampus were activated only among men, and the left amygdala was activated only among women during the task; activation in the apical prefrontal region was significantly greater in men than in women. Our data suggest that the prefrontal region is responsible for the gender differences in the processing of words concerning body image, and may also be responsible for gender differences in susceptibility to eating disorders.

fMRI of alterations in reward selection, anticipation, and feedback in major depressive disorder.

PubMed

Smoski, Moria J; Felder, Jennifer; Bizzell, Joshua; Green, Steven R; Ernst, Monique; Lynch, Thomas R; Dichter, Gabriel S

2009-11-01

The purpose of the present investigation was to evaluate reward processing in unipolar major depressive disorder (MDD). Specifically, we investigated whether adults with MDD demonstrated hyporesponsivity in striatal brain regions and/or hyperresponsivity in cortical brain regions involved in conflict monitoring using a Wheel of Fortune task designed to probe responses during reward selection, reward anticipation, and reward feedback. Functional magnetic resonance imaging (fMRI) data indicated that the MDD group was characterized by reduced activation of striatal reward regions during reward selection, reward anticipation, and reward feedback, supporting previous data indicating hyporesponsivity of reward systems in MDD. Support was not found for hyperresponsivity of cognitive control regions during reward selection or reward anticipation. Instead, MDD participants showed hyperresponsivity in orbitofrontal cortex, a region associated with assessment of risk and reward, during reward selection, as well as decreased activation of the middle frontal gyrus and the rostral cingulate gyrus during reward selection and anticipation. Finally, depression severity was predicted by activation in bilateral midfrontal gyrus during reward selection. Results indicate that MDD is characterized by striatal hyporesponsivity, and that future studies of MDD treatments that seek to improve responses to rewarding stimuli should assess striatal functioning.

Distance-responsive genes found in dancing honey bees.

PubMed

Sen Sarma, M; Rodriguez-Zas, S L; Gernat, T; Nguyen, T; Newman, T; Robinson, G E

2010-10-01

We report that regions of the honey bee brain involved in visual processing and learning and memory show a specific genomic response to distance information. These results were obtained with an established method that separates effects of perceived distance from effects of actual distance flown. Individuals forced to shift from a short to perceived long distance to reach a feeding site showed gene expression differences in the optic lobes and mushroom bodies relative to individuals that continued to perceive a short distance, even though they all flew the same distance. Bioinformatic analyses suggest that the genomic response to distance information involves learning and memory systems associated with well-known signaling pathways, synaptic remodeling, transcription factors and protein metabolism. By showing distance-sensitive brain gene expression, our findings also significantly extend the emerging paradigm of the genome as a dynamic regulator of behavior, that is particularly responsive to stimuli important in social life. © 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Citicoline Affects Appetite and Cortico-Limbic Responses to Images of High Calorie Foods

PubMed Central

Killgore, William D. S.; Ross, Amy J.; Kamiya, Toshi; Kawada, Yoko; Renshaw, Perry F.; Yurgelun-Todd, Deborah A.

2011-01-01

Cytidine-5’-diphosphocholine (citicoline) has a variety of cognitive enhancing, neuroprotective, and neuroregenerative properties. In cocaine-addicted individuals, citicoline has been shown to increase brain dopamine levels and reduce cravings. The effects of this compound on appetite, food cravings, and brain responses to food are unknown. We compared the effects of treatment with citicoline (500 mg/day versus 2000 mg/day) for six weeks on changes in appetite ratings, weight, and cortico-limbic responses to images of high calorie foods using functional magnetic resonance imaging (fMRI). After six weeks, there was no significant change in weight status, although significant declines in appetite ratings were observed for the 2000 mg/day group. The higher dose group also showed significant increases in functional brain responses to food stimuli within the amygdala, insula, and lateral orbitofrontal cortex. Increased activation in these regions correlated with declines in appetite ratings. These preliminary findings suggest a potential usefulness of citicoline in modulating appetite, but further research is warranted. PMID:19260039

Amygdala response to self-critical stimuli and symptom improvement in psychotherapy for depression.

PubMed

Doerig, Nadja; Krieger, Tobias; Altenstein, David; Schlumpf, Yolanda; Spinelli, Simona; Späti, Jakub; Brakowski, Janis; Quednow, Boris B; Seifritz, Erich; Holtforth, Martin Grosse

2016-02-01

Cognitive-behavioural therapy is efficacious in the treatment of major depressive disorder but response rates are still far from satisfactory. To better understand brain responses to individualised emotional stimuli and their association with outcome, to enhance treatment. Functional magnetic resonance imaging data were collected prior to individual psychotherapy. Differences in brain activity during passive viewing of individualised self-critical material in 23 unmedicated out-patients with depression and 28 healthy controls were assessed. The associations between brain activity, cognitive and emotional change, and outcome were analysed in 21 patients. Patients showed enhanced activity in the amygdala and ventral striatum compared with the control group. Non-response to therapy was associated with enhanced activity in the right amygdala compared with those who responded, and activity in this region was negatively associated with outcome. Emotional but not cognitive changes mediated this association. Amygdala hyperactivity may lessen symptom improvement in psychotherapy for depression through attenuating emotional skill acquisition. © The Royal College of Psychiatrists 2016.

Attention training improves aberrant neural dynamics during working memory processing in veterans with PTSD.

PubMed

McDermott, Timothy J; Badura-Brack, Amy S; Becker, Katherine M; Ryan, Tara J; Bar-Haim, Yair; Pine, Daniel S; Khanna, Maya M; Heinrichs-Graham, Elizabeth; Wilson, Tony W

2016-12-01

Posttraumatic stress disorder (PTSD) is associated with executive functioning deficits, including disruptions in working memory (WM). Recent studies suggest that attention training reduces PTSD symptomatology, but the underlying neural mechanisms are unknown. We used high-density magnetoencephalography (MEG) to evaluate whether attention training modulates brain regions serving WM processing in PTSD. Fourteen veterans with PTSD completed a WM task during a 306-sensor MEG recording before and after 8 sessions of attention training treatment. A matched comparison sample of 12 combat-exposed veterans without PTSD completed the same WM task during a single MEG session. To identify the spatiotemporal dynamics, each group's data were transformed into the time-frequency domain, and significant oscillatory brain responses were imaged using a beamforming approach. All participants exhibited activity in left hemispheric language areas consistent with a verbal WM task. Additionally, veterans with PTSD and combat-exposed healthy controls each exhibited oscillatory responses in right hemispheric homologue regions (e.g., right Broca's area); however, these responses were in opposite directions. Group differences in oscillatory activity emerged in the theta band (4-8 Hz) during encoding and in the alpha band (9-12 Hz) during maintenance and were significant in right prefrontal and right supramarginal and inferior parietal regions. Importantly, following attention training, these significant group differences were reduced or eliminated. This study provides initial evidence that attention training improves aberrant neural activity in brain networks serving WM processing.

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

PubMed

Nees, Frauke; Vollstädt-Klein, Sabine; Fauth-Bühler, Mira; Steiner, Sabina; Mann, Karl; Poustka, Luise; Banaschewski, Tobias; Büchel, Christian; Conrod, Patricia J; Garavan, Hugh; Heinz, Andreas; Ittermann, Bernd; Artiges, Eric; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Smolka, Michael N; Struve, Maren; Loth, Eva; Schumann, Gunter; Flor, Herta

2012-11-01

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

Gain in Body Fat Is Associated with Increased Striatal Response to Palatable Food Cues, whereas Body Fat Stability Is Associated with Decreased Striatal Response

PubMed Central

Yokum, Sonja

2016-01-01

Cross-sectional brain-imaging studies reveal that obese versus lean humans show greater responsivity of reward and attention regions to palatable food cues, but lower responsivity of reward regions to palatable food receipt. However, these individual differences in responsivity may result from a period of overeating. We conducted a repeated-measures fMRI study to test whether healthy weight adolescent humans who gained body fat over a 2 or 3 year follow-up period show an increase in responsivity of reward and attention regions to a cue signaling impending milkshake receipt and a simultaneous decrease in responsivity of reward regions to milkshake receipt versus adolescents who showed stability of or loss of body fat. Adolescents who gained body fat, who largely remained in a healthy weight range, showed increases in activation in the putamen, mid-insula, Rolandic operculum, and precuneus to a cue signaling impending milkshake receipt versus those who showed stability of or loss of body fat, though these effects were partially driven by reductions in responsivity among the latter groups. Adolescents who gained body fat reported significantly greater milkshake wanting and milkshake pleasantness ratings at follow-up compared to those who lost body fat. Adolescents who gained body fat did not show a reduction in responsivity of reward regions to milkshake receipt or changes in responsivity to receipt and anticipated receipt of monetary reward. Data suggest that initiating a prolonged period of overeating may increase striatal responsivity to food cues, and that maintaining a balance between caloric intake and expenditure may reduce striatal, insular, and Rolandic operculum responsivity. SIGNIFICANCE STATEMENT This novel, repeated-measures brain-imaging study suggests that adolescents who gained body fat over our follow-up period experienced an increase in striatal responsivity to cues for palatable foods compared to those who showed stability of or loss of body fat. Results also imply that maintaining a balance between caloric intake and expenditure over time may reduce striatal, insular, and Rolandic operculum responsivity to food cues, which might decrease risk for future overeating. PMID:27358453

A quantitative and qualitative review of the effects of testosterone on the function and structure of the human social-emotional brain.

PubMed

Heany, Sarah J; van Honk, Jack; Stein, Dan J; Brooks, Samantha J

2016-02-01

Social and affective research in humans is increasingly using functional and structural neuroimaging techniques to aid the understanding of how hormones, such as testosterone, modulate a wide range of psychological processes. We conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of testosterone administration, and of fMRI studies that measured endogenous levels of the hormone, in relation to social and affective stimuli. Furthermore, we conducted a review of structural MRI i.e. voxel based morphometry (VBM) studies which considered brain volume in relation to testosterone levels in adults and in children. In the included testosterone administration fMRI studies, which consisted of female samples only, bilateral amygdala/parahippocampal regions as well as the right caudate were significantly activated by social-affective stimuli in the testosterone condition. In the studies considering endogenous levels of testosterone, stimuli-invoked activations relating to testosterone levels were noted in the bilateral amygdala/parahippocampal regions and the brainstem. When the endogenous testosterone studies were split by sex, the significant activation of the brain stem was seen in the female samples only. Significant stimuli-invoked deactivations relating to endogenous testosterone levels were also seen in the right and left amygdala/parahippocampal regions studies. The findings of the VBM studies were less consistent. In adults larger volumes in the limbic and temporal regions were associated with higher endogenous testosterone. In children, boys showed a positive correlation between testosterone and brain volume in many regions, including the amygdala, as well as global grey matter volume, while girls showed a neutral or negative association between testosterone levels and many brain volumes. In conclusion, amygdalar and parahippocampal regions appear to be key target regions for the acute actions of testosterone in response to social and affective stimuli, while neurodevelopmentally the volumes of a broader network of brain structures are associated with testosterone levels in a sexually dimorphic manner.

The functional highly sensitive brain: a review of the brain circuits underlying sensory processing sensitivity and seemingly related disorders.

PubMed

Acevedo, Bianca; Aron, Elaine; Pospos, Sarah; Jessen, Dana

2018-04-19

During the past decade, research on the biological basis of sensory processing sensitivity (SPS)-a genetically based trait associated with greater sensitivity and responsivity to environmental and social stimuli-has burgeoned. As researchers try to characterize this trait, it is still unclear how SPS is distinct from seemingly related clinical disorders that have overlapping symptoms, such as sensitivity to the environment and hyper-responsiveness to incoming stimuli. Thus, in this review, we compare the neural regions implicated in SPS with those found in fMRI studies of-Autism Spectrum Disorder (ASD), Schizophrenia (SZ) and Post-Traumatic Stress Disorder (PTSD) to elucidate the neural markers and cardinal features of SPS versus these seemingly related clinical disorders. We propose that SPS is a stable trait that is characterized by greater empathy, awareness, responsivity and depth of processing to salient stimuli. We conclude that SPS is distinct from ASD, SZ and PTSD in that in response to social and emotional stimuli, SPS differentially engages brain regions involved in reward processing, memory, physiological homeostasis, self-other processing, empathy and awareness. We suggest that this serves species survival via deep integration and memory for environmental and social information that may subserve well-being and cooperation.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'. © 2018 The Authors.

Reversal of dopamine system dysfunction in response to high-fat diet.

PubMed

Carlin, Jesselea; Hill-Smith, Tiffany E; Lucki, Irwin; Reyes, Teresa M

2013-12-01

To test whether high-fat diet (HFD) decreases dopaminergic tone in reward regions of the brain and evaluate whether these changes reverse after removal of the HFD. Male and female mice were fed a 60% HFD for 12 weeks. An additional group was evaluated 4 weeks after removal of the HFD. These groups were compared with control fed, age-matched controls. Sucrose and saccharin preference was measured along with mRNA expression of dopamine (DA)-related genes by Real Time-quantitative PCR (RT-qPCR). DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using high-performance liquid chromatography. DNA methylation of the dopamine transporter (DAT) promoter was measured by methylated DNA immunoprecipitation and RT-qPCR. After chronic HFD, sucrose preference was reduced, and then normalized after removal of the HFD. Decreased expression of DA genes, decreased DA content and alterations in DAT promoter methylation, was observed. Importantly, response to HFD and the persistence of changes depended on sex and brain region. These data identify diminished DA tone after early-life chronic HFD with a complex pattern of reversal and persistence that varies by both sex and brain region. Central nervous system changes that did not reverse after HFD withdrawal may contribute to the difficulty in maintaining weight-loss after diet intervention. Copyright © 2013 The Obesity Society.

Stress modulation of cognitive and affective processes

PubMed Central

CAMPEAU, SERGE; LIBERZON, ISRAEL; MORILAK, DAVID; RESSLER, KERRY

2012-01-01

This review summarizes the major discussion points of a symposium on stress modulation of cognitive and affective processes, which was held during the 2010 workshop on the neurobiology of stress (Boulder, CO, USA). The four discussants addressed a number of specific cognitive and affective factors that are modulated by exposure to acute or repeated stress. Dr David Morilak discussed the effects of various repeated stress situations on cognitive flexibility, as assessed with a rodent model of attentional set-shifting task, and how performance on slightly different aspects of this test is modulated by different prefrontal regions through monoaminergic neurotransmission. Dr Serge Campeau summarized the findings of several studies exploring a number of factors and brain regions that regulate habituation of various autonomic and neuroendocrine responses to repeated audiogenic stress exposures. Dr Kerry Ressler discussed a body of work exploring the modulation and extinction of fear memories in rodents and humans, especially focusing on the role of key neurotransmitter systems including excitatory amino acids and brain-derived neurotrophic factor. Dr Israel Liberzon presented recent results on human decision-making processes in response to exogenous glucocorticoid hormone administration. Overall, these discussions are casting a wider framework on the cognitive/affective processes that are distinctly regulated by the experience of stress and some of the brain regions and neurotransmitter systems associated with these effects. PMID:21790481

Physiological self-regulation of regional brain activity using real-time functional magnetic resonance imaging (fMRI): methodology and exemplary data.

PubMed

Weiskopf, Nikolaus; Veit, Ralf; Erb, Michael; Mathiak, Klaus; Grodd, Wolfgang; Goebel, Rainer; Birbaumer, Niels

2003-07-01

A brain-computer interface (BCI) based on real-time functional magnetic resonance imaging (fMRI) is presented which allows human subjects to observe and control changes of their own blood oxygen level-dependent (BOLD) response. This BCI performs data preprocessing (including linear trend removal, 3D motion correction) and statistical analysis on-line. Local BOLD signals are continuously fed back to the subject in the magnetic resonance scanner with a delay of less than 2 s from image acquisition. The mean signal of a region of interest is plotted as a time-series superimposed on color-coded stripes which indicate the task, i.e., to increase or decrease the BOLD signal. We exemplify the presented BCI with one volunteer intending to control the signal of the rostral-ventral and dorsal part of the anterior cingulate cortex (ACC). The subject achieved significant changes of local BOLD responses as revealed by region of interest analysis and statistical parametric maps. The percent signal change increased across fMRI-feedback sessions suggesting a learning effect with training. This methodology of fMRI-feedback can assess voluntary control of circumscribed brain areas. As a further extension, behavioral effects of local self-regulation become accessible as a new field of research.

Intraoperative Functional Ultrasound Imaging of Human Brain Activity.

PubMed

Imbault, Marion; Chauvet, Dorian; Gennisson, Jean-Luc; Capelle, Laurent; Tanter, Mickael

2017-08-04

The functional mapping of brain activity is essential to perform optimal glioma surgery and to minimize the risk of postoperative deficits. We introduce a new, portable neuroimaging modality of the human brain based on functional ultrasound (fUS) for deep functional cortical mapping. Using plane-wave transmissions at an ultrafast frame rate (1 kHz), fUS is performed during surgery to measure transient changes in cerebral blood volume with a high spatiotemporal resolution (250 µm, 1 ms). fUS identifies, maps and differentiates regions of brain activation during task-evoked cortical responses within the depth of a sulcus in both awake and anaesthetized patients.

The change of the brain activation patterns as children learn algebra equation solving

NASA Astrophysics Data System (ADS)

Qin, Yulin; Carter, Cameron S.; Silk, Eli M.; Stenger, V. Andrew; Fissell, Kate; Goode, Adam; Anderson, John R.

2004-04-01

In a brain imaging study of children learning algebra, it is shown that the same regions are active in children solving equations as are active in experienced adults solving equations. As with adults, practice in symbol manipulation produces a reduced activation in prefrontal cortex area. However, unlike adults, practice seems also to produce a decrease in a parietal area that is holding an image of the equation. This finding suggests that adolescents' brain responses are more plastic and change more with practice. These results are integrated in a cognitive model that predicts both the behavioral and brain imaging results.