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New applications of laser microbeam irradiation to cell and developmental biology include a new instrument with a tunable wavelength (217- to 800-nanometer) laser microbeam and a wide range of energies and exposure durations (down to 25 X 10(-12) second). Laser microbeams can be used for microirradiation of selected nucleolar genetic regions and for laser microdissection of mitotic and cytoplasmic organelles. They are also used to disrupt the developing neurosensory appendages of the cricket and the imaginal discs of Drosophila.

A computer-based tracing technique has been developed to follow the movement of living cells and keep them centered in the field of view of an optical microscope. With the use of an image-processing system, the video image of a cell can be sufficiently processed to allow computer-recognition of the cell boundaries. Determination of the location of the center of the cell enables comparison of successive cell positions and correction for any cell movement. In order to illustrate the versatility of this technique, patterns of movement were obtained of cancerous and non-cancerous cells in an effort to determine the difference in motility between the two cell types. After examination of the data gathered, it was found that there is no difference in the motility between the two cell types over 1-h periods.

fMRI has been increasingly used to study brain function in domestic dogs trained to lie still in MRI scanners. These studies highlight both similarities and differences between dogs and humans when presented with the same stimuli, raising intriguing questions about the concept of functional homologies in a coevolved species that shares the human environment., Competing Interests: Declaration of interests The author declares no competing interests in relation to this work., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Recent advancements using machine learning and functional magnetic resonance imaging (fMRI) to decode visual stimuli from the human and nonhuman cortex have resulted in new insights into the nature of perception. However, this approach has yet to be applied substantially to animals other than primates, raising questions about the nature of such representations across the animal kingdom. Here, we used awake fMRI in two domestic dogs and two humans, obtained while each watched specially created dog-appropriate naturalistic videos. We then trained a neural net (Ivis) to classify the video content from a total of 90 min of recorded brain activity from each. We tested both an object-based classifier, attempting to discriminate categories such as dog, human, and car, and an action-based classifier, attempting to discriminate categories such as eating, sniffing, and talking. Compared to the two human subjects, for whom both types of classifier performed well above chance, only action-based classifiers were successful in decoding video content from the dogs. These results demonstrate the first known application of machine learning to decode naturalistic videos from the brain of a carnivore and suggest that the dog's-eye view of the world may be quite different from our own.

Post-mortem magnetic resonance imaging (MRI) provides the opportunity to acquire high-resolution datasets to investigate neuroanatomy and validate the origins of image contrast through microscopy comparisons. We introduce the Digital Brain Bank (open.win.ox.ac.uk/DigitalBrainBank), a data release platform providing open access to curated, multimodal post-mortem neuroimaging datasets. Datasets span three themes -Digital Neuroanatomist : datasets for detailed neuroanatomical investigations; Digital Brain Zoo : datasets for comparative neuroanatomy; and Digital Pathologist : datasets for neuropathology investigations. The first Digital Brain Bank data release includes 21 distinctive whole-brain diffusion MRI datasets for structural connectivity investigations, alongside microscopy and complementary MRI modalities. This includes one of the highest-resolution whole-brain human diffusion MRI datasets ever acquired, whole-brain diffusion MRI in fourteen nonhuman primate species, and one of the largest post-mortem whole-brain cohort imaging studies in neurodegeneration. The Digital Brain Bank is the culmination of our lab's investment into post-mortem MRI methodology and MRI-microscopy analysis techniques. This manuscript provides a detailed overview of our work with post-mortem imaging to date, including the development of diffusion MRI methods to image large post-mortem samples, including whole, human brains. Taken together, the Digital Brain Bank provides cross-scale, cross-species datasets facilitating the incorporation of post-mortem data into neuroimaging studies., Competing Interests: BT, TH, OA, SB, GB, MB, KB, SF, Mv, AH, IH, AK, AL, PM, RM, JM, DM, MP, LR, JS, LS, CS, AS, MT, CW, RM No competing interests declared, SJ, KM Reviewing editor, eLife, (© 2022, Tendler et al.)

Previous research to localize face areas in dogs' brains has generally relied on static images or videos. However, most dogs do not naturally engage with two-dimensional images, raising the question of whether dogs perceive such images as representations of real faces and objects. To measure the equivalency of live and two-dimensional stimuli in the dog's brain, during functional magnetic resonance imaging (fMRI) we presented dogs and humans with live-action stimuli (actors and objects) as well as videos of the same actors and objects. The dogs ( n = 7) and humans ( n = 5) were presented with 20 s blocks of faces and objects in random order. In dogs, we found significant areas of increased activation in the putative dog face area, and in humans, we found significant areas of increased activation in the fusiform face area to both live and video stimuli. In both dogs and humans, we found areas of significant activation in the posterior superior temporal sulcus (ectosylvian fissure in dogs) and the lateral occipital complex (entolateral gyrus in dogs) to both live and video stimuli. Of these regions of interest, only the area along the ectosylvian fissure in dogs showed significantly more activation to live faces than to video faces, whereas, in humans, both the fusiform face area and posterior superior temporal sulcus responded significantly more to live conditions than video conditions. However, using the video conditions alone, we were able to localize all regions of interest in both dogs and humans. Therefore, videos can be used to localize these regions of interest, though live conditions may be more salient.

Given humans' habitual use of screens, they rarely consider potential differences when viewing two-dimensional (2D) stimuli and real-world versions of dimensional stimuli. Dogs also have access to many forms of screens and touchpads, with owners even subscribing to dog-directed content. Humans understand that 2D stimuli are representations of real-world objects, but do dogs? In canine cognition studies, 2D stimuli are almost always used to study what is normally 3D, like faces, and may assume that both 2D and 3D stimuli are represented in the brain the same way. Here, we used awake fMRI in 15 dogs to examine the neural mechanisms underlying dogs' perception of two- and three-dimensional objects after the dogs were trained on either two- or three-dimensional versions of the objects. Activation within reward processing regions and parietal cortex of the dog brain to 2D and 3D versions of objects was determined by their training experience, as dogs trained on one dimensionality showed greater differential activation within the dimension on which they were trained. These results show that dogs do not automatically generalize between two- and three-dimensional versions of object stimuli and suggest that future research consider the implicit assumptions when using pictures or videos., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The perception and representation of objects in the world are foundational to all animals. The relative importance of objects' physical properties versus how the objects are interacted with continues to be debated. Neural evidence in humans and nonhuman primates suggests animate-inanimate and face-body dimensions of objects are represented in the temporal cortex. However, because primates have opposable thumbs and interact with objects in similar ways, the question remains as to whether this similarity represents the evolution of a common cognitive process or whether it reflects a similarity of physical interaction. Here, we used functional magnetic resonance imaging (fMRI) in dogs to test whether the type of interaction affects object processing in an animal that interacts primarily with its mouth. In Study 1, we identified object-processing regions of cortex by having dogs passively view movies of faces and objects. In Study 2, dogs were trained to interact with two new objects with either the mouth or the paw. Then, we measured responsivity in the object regions to the presentation of these objects. Mouth-objects elicited significantly greater activity in object regions than paw-objects. Mouth-objects were also associated with activity in somatosensory cortex, suggesting dogs were anticipating mouthing interactions. These findings suggest that object perception in dogs is affected by how dogs expect to interact with familiar objects., (© 2021 Wiley Periodicals LLC.)

Background: Domoic acid (DOM) is a neurotoxin produced by some harmful algae blooms in coastal waters. California sea lions (Zalophus californianus) exposed to DOM often strand on beaches where they exhibit a variety of symptoms, including seizures. These animals typically show hippocampal atrophy on MRI scans., New Method: We describe an MRI protocol for comprehensive evaluation of DOM toxicosis in the sea lion brain. We intend to study brain development in pups exposed in utero. The protocol depicts the hippocampal formation as the primary region of interest. We include scans for quantitative morphometry, functional and structural connectivity, and a cerebral blood flow map., Results: High-resolution 3D anatomical scans facilitate post hoc slicing in arbitrary planes and accurate morphometry. We demonstrate the first cerebral blood flow map using MRI, and the first structural tractography from a live sea lion brain., Comparison With Existing Methods: Scans were compared to prior anatomical and functional studies in live sea lions, and structural connectivity in post mortem specimens. Hippocampal volumes were broadly in line with prior studies, with differences likely attributable to the 3D approach used here. Functional connectivity of the dorsal left hippocampus matched that found in a prior study conducted at a lower magnetic field, while structural connectivity in the live brain agreed with findings observed in post mortem studies., Conclusions: Our protocol provides a comprehensive, longitudinal view of the functional and anatomical changes expected to result from DOM toxicosis. It can also screen for other common neurological pathologies and is suitable for any pinniped that can fit inside an MRI scanner., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In working and practical contexts, dogs rely upon their ability to discriminate a target odor from distracting odors and other sensory stimuli. Using awake functional magnetic resonance imaging (fMRI) in 18 dogs, we examined the neural mechanisms underlying odor discrimination between 2 odors and a mixture of the odors. Neural activation was measured during the presentation of a target odor (A) associated with a food reward, a distractor odor (B) associated with nothing, and a mixture of the two odors (A+B). Changes in neural activation during the presentations of the odor stimuli in individual dogs were measured over time within three regions known to be involved with odor processing: the caudate nucleus, the amygdala, and the olfactory bulbs. Average activation within the amygdala showed that dogs maximally differentiated between odor stimuli based on the stimulus-reward associations by the first run, while activation to the mixture (A+B) was most similar to the no-reward (B) stimulus. To clarify the neural representation of odor mixtures in the dog brain, we used a random forest classifier to compare multilabel (elemental) versus multiclass (configural) models. The multiclass model performed much better than the multilabel (weighted-F1 0.44 vs. 0.14), suggesting the odor mixture was processed configurally. Analysis of the subset of high-performing dogs' brain classification metrics revealed a network of olfactory information-carrying brain regions that included the amygdala, piriform cortex, and posterior cingulate. These results add further evidence for the configural processing of odor mixtures in dogs and suggest a novel way to identify high-performers based on brain classification metrics., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The approximate number system (ANS), which supports the rapid estimation of quantity, emerges early in human development and is widespread across species. Neural evidence from both human and non-human primates suggests the parietal cortex as a primary locus of numerical estimation, but it is unclear whether the numerical competencies observed across non-primate species are subserved by similar neural mechanisms. Moreover, because studies with non-human animals typically involve extensive training, little is known about the spontaneous numerical capacities of non-human animals. To address these questions, we examined the neural underpinnings of number perception using awake canine functional magnetic resonance imaging. Dogs passively viewed dot arrays that varied in ratio and, critically, received no task-relevant training or exposure prior to testing. We found evidence of ratio-dependent activation, which is a key feature of the ANS, in canine parietotemporal cortex in the majority of dogs tested. This finding is suggestive of a neural mechanism for quantity perception that has been conserved across mammalian evolution.

How do dogs understand human words? At a basic level, understanding would require the discrimination of words from non-words. To determine the mechanisms of such a discrimination, we trained 12 dogs to retrieve two objects based on object names, then probed the neural basis for these auditory discriminations using awake-fMRI. We compared the neural response to these trained words relative to "oddball" pseudowords the dogs had not heard before. Consistent with novelty detection, we found greater activation for pseudowords relative to trained words bilaterally in the parietotemporal cortex. To probe the neural basis for representations of trained words, searchlight multivoxel pattern analysis (MVPA) revealed that a subset of dogs had clusters of informative voxels that discriminated between the two trained words. These clusters included the left temporal cortex and amygdala, left caudate nucleus, and thalamus. These results demonstrate that dogs' processing of human words utilizes basic processes like novelty detection, and for some dogs, may also include auditory and hedonic representations.

Dogs may follow their nose, but they learn associations to many types of sensory stimuli. Are some modalities learned better than others? We used awake fMRI in 19 dogs over a series of three experiments to measure reward-related learning of visual, olfactory, and verbal stimuli. Neurobiological learning curves were generated for individual dogs by measuring activation over time within three regions of interest: the caudate nucleus, amygdala, and parietotemporal cortex. The learning curves showed that dogs formed stimulus-reward associations in as little as 22 trials. Consistent with neuroimaging studies of associative learning, the caudate showed a main effect for reward-related stimuli, but not a significant interaction with modality. However, there were significant differences in the time courses, suggesting that although multiple modalities are represented in the caudate, the rates of acquisition and habituation are modality-dependent and are potentially gated by their salience in the amygdala. Visual and olfactory modalities resulted in the fastest learning, while verbal stimuli were least effective, suggesting that verbal commands may be the least efficient way to train dogs.

Training dogs for awake-MRI began in 2012 for the study of canine cognition. Although originally envisioned as a research technique to understand the neural mechanisms of canine cognitive function, its potential as a new diagnostic clinical tool has become apparent. A high-quality structural scan of the brain can be acquired without sedation or anesthesia in as little as 30 s in a well-trained dog. This has opened the possibility of longitudinal imaging of CNS disease with MRI both as a means of monitoring treatment and potentially as a surveillance tool for inflammatory and neoplastic brain diseases in high-risk breeds. This same training can be used to image other body regions, such as the abdomen, enabling clinicians to screen for abdominal disease using cross sectional imaging without the need for anesthesia and without exposing the patient to ionizing radiation. We present four examples of dogs trained for awake-MRI who developed: (1) nasal carcinoma; (2) brain tumor; (3) abdominal lipoma; (4) idiopathic epilepsy.

Hundreds of wild California sea lions (Zalophus californianus) exposed to the algal neurotoxin domoic acid are treated in veterinary rehabilitation centers each year. Common chronic effects of toxic exposure in these animals are seizures and hippocampal damage, and they have been proposed as a natural animal model for human epilepsy. Humans with medial temporal lobe epilepsy present with white matter pathology in a number of tracts including the fornix and increased structural connectivity between the hippocampus and thalamus. However, there are no prior data on structural connectivity in sea lion brains, with or without neuropathology. In the present study, we used a novel diffusion tensor imaging technique to obtain high resolution (1mm isotropic) white matter maps in brains obtained opportunistically postmortem from wild sea lions with and without chronic clinical signs of toxic exposure to domoic acid. All animals had received a full veterinary workup and diagnosis prior to euthanasia. We measured hippocampal atrophy morphometrically, and all brains were examined histopathologically. In animals diagnosed with chronic domoic acid toxicosis, the fornix showed signs of altered diffusion properties indicative of pathology; these brains also had increased structural connectivity between hippocampus and thalamus in comparison to brains from animals with no neurological signs. These findings establish further parallels between human medial temporal lobe epilepsy and a naturally occurring condition in wild sea lions and simultaneously advance general knowledge of the deleterious effects of an increasingly common natural toxin., (© 2017 Wiley Periodicals, Inc.)

Background: Commonly observed distortions in decision-making among patients with major depressive disorder (MDD) may emerge from impaired reward processing and cognitive biases toward negative events. There is substantial theoretical support for the hypothesis that MDD patients overweight potential losses compared with gains, though the neurobiological underpinnings of this bias are uncertain., Methods: Twenty-one unmedicated patients with MDD were compared with 25 healthy controls (HC) using functional magnetic resonance imaging (fMRI) together with an economic decision-making task over mixed lotteries involving probabilistic gains and losses. Region-of-interest analyses evaluated neural signatures of gain and loss coding within a core network of brain areas known to be involved in valuation (anterior insula, caudate nucleus, ventromedial prefrontal cortex)., Results: Usable fMRI data were available for 19 MDD and 23 HC subjects. Anterior insula signal showed negative coding of losses (gain > loss) in HC subjects consistent with previous findings, whereas MDD subjects demonstrated significant reversals in these associations (loss > gain). Moreover, depression severity further enhanced the positive coding of losses in anterior insula, ventromedial prefrontal cortex, and caudate nucleus. The hyper-responsivity to losses displayed by the anterior insula of MDD patients was paralleled by a reduced influence of gain, but not loss, stake size on choice latencies., Conclusions: Patients with MDD demonstrate a significant shift from negative to positive coding of losses in the anterior insula, revealing the importance of this structure in value-based decision-making in the context of emotional disturbances.

The overall goal of this work was to measure the efficacy of fMRI for predicting whether a dog would be a successful service dog. The training and imaging were performed in 49 dogs entering service training at 17-21 months of age. 33 dogs completed service training and were matched with a person, while 10 were released for behavioral reasons (4 were selected as breeders and 2 were released for medical reasons.) After 2 months of training, fMRI responses were measured while each dog observed hand signals indicating either reward or no reward and given by both a familiar handler and a stranger. Using anatomically defined ROIs in the caudate, amygdala, and visual cortex, we developed a classifier based on the dogs' subsequent training outcomes. The classifier had a positive predictive value of 94% and a negative predictive value of 67%. The area under the ROC curve was 0.91 (0.80 with 4-fold cross-validation, P = 0.01), indicating a significant predictive capability. The magnitude of response in the caudate was positively correlated with a successful outcome, while the response in the amygdala depended on the interaction with the visual cortex during the stranger condition and was negatively correlated with outcome (higher being associated with failure). These results suggest that, as indexed by caudate activity, successful service dogs generalize associations to hand signals regardless who gives them but without excessive arousal as measured in the amygdala.

The last known Tasmanian tiger (Thylacinus cynocephalus)-aka the thylacine-died in 1936. Because its natural behavior was never scientifically documented, we are left to infer aspects of its behavior from museum specimens and historical recollections of bushmen. Recent advances in brain imaging have made it possible to scan postmortem specimens of a wide range of animals, even more than a decade old. Any thylacine brain, however, would be more than 100 years old. Here, we show that it is possible to reconstruct white matter tracts in two thylacine brains. For functional interpretation, we compare to the white matter reconstructions of the brains of two Tasmanian devils (Sarcophilus harrisii). We reconstructed the cortical projection zones of the basal ganglia and major thalamic nuclei. The basal ganglia reconstruction showed a more modularized pattern in the cortex of the thylacine, while the devil cortex was dominated by the putamen. Similarly, the thalamic projections had a more orderly topography in the thylacine than the devil. These results are consistent with theories of brain evolution suggesting that larger brains are more modularized. Functionally, the thylacine's brain may have had relatively more cortex devoted to planning and decision-making, which would be consistent with a predatory ecological niche versus the scavenging niche of the devil., Competing Interests: The authors have declared that no competing interests exist.

Dogs are hypersocial with humans, and their integration into human social ecology makes dogs a unique model for studying cross-species social bonding. However, the proximal neural mechanisms driving dog-human social interaction are unknown. We used functional magnetic resonance imaging in 15 awake dogs to probe the neural basis for their preferences for social interaction and food reward. In a first experiment, we used the ventral caudate as a measure of intrinsic reward value and compared activation to conditioned stimuli that predicted food, praise or nothing. Relative to the control stimulus, the caudate was significantly more active to the reward-predicting stimuli and showed roughly equal or greater activation to praise vs food in 13 of 15 dogs. To confirm that these differences were driven by the intrinsic value of social praise, we performed a second imaging experiment in which the praise was withheld on a subset of trials. The difference in caudate activation to the receipt of praise, relative to its withholding, was strongly correlated with the differential activation to the conditioned stimuli in the first experiment. In a third experiment, we performed an out-of-scanner choice task in which the dog repeatedly selected food or owner in a Y-maze. The relative caudate activation to food- and praise-predicting stimuli in Experiment 1 was a strong predictor of each dog's sequence of choices in the Y-maze. Analogous to similar neuroimaging studies of individual differences in human social reward, our findings demonstrate a neural mechanism for preference in domestic dogs that is stable within, but variable between, individuals. Moreover, the individual differences in the caudate responses indicate the potentially higher value of social than food reward for some dogs and may help to explain the apparent efficacy of social interaction in dog training., (© The Author (2016). Published by Oxford University Press.)

Recent behavioral evidence suggests that dogs, like humans and monkeys, are capable of visual face recognition. But do dogs also exhibit specialized cortical face regions similar to humans and monkeys? Using functional magnetic resonance imaging (fMRI) in six dogs trained to remain motionless during scanning without restraint or sedation, we found a region in the canine temporal lobe that responded significantly more to movies of human faces than to movies of everyday objects. Next, using a new stimulus set to investigate face selectivity in this predefined candidate dog face area, we found that this region responded similarly to images of human faces and dog faces, yet significantly more to both human and dog faces than to images of objects. Such face selectivity was not found in dog primary visual cortex. Taken together, these findings: (1) provide the first evidence for a face-selective region in the temporal cortex of dogs, which cannot be explained by simple low-level visual feature extraction; (2) reveal that neural machinery dedicated to face processing is not unique to primates; and (3) may help explain dogs' exquisite sensitivity to human social cues.

The brains of odontocetes (toothed whales) look grossly different from their terrestrial relatives. Because of their adaptation to the aquatic environment and their reliance on echolocation, the odontocetes' auditory system is both unique and crucial to their survival. Yet, scant data exist about the functional organization of the cetacean auditory system. A predominant hypothesis is that the primary auditory cortex lies in the suprasylvian gyrus along the vertex of the hemispheres, with this position induced by expansion of 'associative' regions in lateral and caudal directions. However, the precise location of the auditory cortex and its connections are still unknown. Here, we used a novel diffusion tensor imaging (DTI) sequence in archival post-mortem brains of a common dolphin (Delphinus delphis) and a pantropical dolphin (Stenella attenuata) to map their sensory and motor systems. Using thalamic parcellation based on traditionally defined regions for the primary visual (V1) and auditory cortex (A1), we found distinct regions of the thalamus connected to V1 and A1. But in addition to suprasylvian-A1, we report here, for the first time, the auditory cortex also exists in the temporal lobe, in a region near cetacean-A2 and possibly analogous to the primary auditory cortex in related terrestrial mammals (Artiodactyla). Using probabilistic tract tracing, we found a direct pathway from the inferior colliculus to the medial geniculate nucleus to the temporal lobe near the sylvian fissure. Our results demonstrate the feasibility of post-mortem DTI in archival specimens to answer basic questions in comparative neurobiology in a way that has not previously been possible and shows a link between the cetacean auditory system and those of terrestrial mammals. Given that fresh cetacean specimens are relatively rare, the ability to measure connectivity in archival specimens opens up a plethora of possibilities for investigating neuroanatomy in cetaceans and other species.

Understanding dogs' perceptual experience of both conspecifics and humans is important to understand how dogs evolved and the nature of their relationships with humans and other dogs. Olfaction is believed to be dogs' most powerful and perhaps important sense and an obvious place to begin for the study of social cognition of conspecifics and humans. We used fMRI in a cohort of dogs (N=12) that had been trained to remain motionless while unsedated and unrestrained in the MRI. By presenting scents from humans and conspecifics, we aimed to identify the dimensions of dogs' responses to salient biological odors - whether they are based on species (dog or human), familiarity, or a specific combination of factors. We focused our analysis on the dog's caudate nucleus because of its well-known association with positive expectations and because of its clearly defined anatomical location. We hypothesized that if dogs' primary association to reward, whether it is based on food or social bonds, is to humans, then the human scents would activate the caudate more than the conspecific scents. Conversely, if the smell of conspecifics activated the caudate more than the smell of humans, dogs' association to reward would be stronger to their fellow canines. Five scents were presented (self, familiar human, strange human, familiar dog, strange dog). While the olfactory bulb/peduncle was activated to a similar degree by all the scents, the caudate was activated maximally to the familiar human. Importantly, the scent of the familiar human was not the handler, meaning that the caudate response differentiated the scent in the absence of the person being present. The caudate activation suggested that not only did the dogs discriminate that scent from the others, they had a positive association with it. This speaks to the power of the dog's sense of smell, and it provides important clues about the importance of humans in dogs' lives. This article is part of a Special Issue entitled: Canine Behavior., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Having previously used functional MRI to map the response to a reward signal in the ventral caudate in awake unrestrained dogs, here we examined the importance of signal source to canine caudate activation. Hand signals representing either incipient reward or no reward were presented by a familiar human (each dog's respective handler), an unfamiliar human, and via illustrated images of hands on a computer screen to 13 dogs undergoing voluntary fMRI. All dogs had received extensive training with the reward and no-reward signals from their handlers and with the computer images and had minimal exposure to the signals from strangers. All dogs showed differentially higher BOLD response in the ventral caudate to the reward versus no reward signals, and there was a robust effect at the group level. Further, differential response to the signal source had a highly significant interaction with a dog's general aggressivity as measured by the C-BARQ canine personality assessment. Dogs with greater aggressivity showed a higher differential response to the reward signal versus no-reward signal presented by the unfamiliar human and computer, while dogs with lower aggressivity showed a higher differential response to the reward signal versus no-reward signal from their handler. This suggests that specific facets of canine temperament bear more strongly on the perceived reward value of relevant communication signals than does reinforcement history, as each of the dogs were reinforced similarly for each signal, regardless of the source (familiar human, unfamiliar human, or computer). A group-level psychophysiological interaction (PPI) connectivity analysis showed increased functional coupling between the caudate and a region of cortex associated with visual discrimination and learning on reward versus no-reward trials. Our findings emphasize the sensitivity of the domestic dog to human social interaction, and may have other implications and applications pertinent to the training and assessment of working and pet dogs.

Previously, we demonstrated the possibility of fMRI in two awake and unrestrained dogs. Here, we determined the replicability and heterogeneity of these results in an additional 11 dogs for a total of 13 subjects. Based on an anatomically placed region-of-interest, we compared the caudate response to a hand signal indicating the imminent availability of a food reward to a hand signal indicating no reward. 8 of 13 dogs had a positive differential caudate response to the signal indicating reward. The mean differential caudate response was 0.09%, which was similar to a comparable human study. These results show that canine fMRI is reliable and can be done with minimal stress to the dogs.

There are two regularities we have learned from experimental studies of choice under risk. The first is that the majority of people weigh objective probabilities non-linearly. The second regularity, although less commonly acknowledged, is that there is a large amount of heterogeneity in how people distort probabilities. Despite of this, little effort has been made to identify the source of heterogeneity. In this paper, we explore the possibility that personality type is linked to probability distortions. Using validated psychological questionnaires, we clustered participants into distinct personality types: motivated, impulsive, and affective. We found that the motivated viewed gambling more attractive, whereas the impulsive were the most capable of discriminating non-extreme probabilities. Our results suggest that the observed heterogeneity in probability distortions may be explained by personality profiles, which can be elicited though standard psychological questionnaires.

There is mounting evidence that the mesolimbic dopamine system carries valuation signals not only for appetitive or gain-related stimuli, with which it is traditionally associated, but also for aversive and loss-related stimuli. Cellular-level studies demonstrate that the neuronal architecture to support aversive stimuli encoding in this system does exist. Both cellular-level and human neuroimaging research suggest the co-existence of appetitive and aversive prediction-error signals within the mesocorticolimbic system. These findings shift the view of the mesocorticolimbic system as a singular pathway for reward to a system with multiple signals across a wide range of domains that drive value-based decision making., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We sought to determine whether reading a novel causes measurable changes in resting-state connectivity of the brain and how long these changes persist. Incorporating a within-subjects design, participants received resting-state functional magnetic resonance imaging scans on 19 consecutive days. First, baseline resting state data for a "washin" period were taken for each participant for 5 days. For the next 9 days, participants read 1/9th of a novel during the evening and resting-state data were taken the next morning. Finally, resting-state data for a "wash-out" period were taken for 5 days after the conclusion of the novel. On the days after the reading, significant increases in connectivity were centered on hubs in the left angular/supramarginal gyri and right posterior temporal gyri. These hubs corresponded to regions previously associated with perspective taking and story comprehension, and the changes exhibited a timecourse that decayed rapidly after the completion of the novel. Long-term changes in connectivity, which persisted for several days after the reading, were observed in bilateral somatosensory cortex, suggesting a potential mechanism for "embodied semantics."

We investigated behavioral and neurobiological mechanisms by which risk-averse advice, provided by an expert, affected risky decisions across three developmental groups [early adolescents (12-14 years), late adolescents (15-17 years), adults (18+ years)]. Using cumulative prospect theory, we modeled choice behavior during a risky-choice task. Results indicate that advice had a significantly greater impact on risky choice in both adolescent groups than in adults. Using functional magnetic resonance imaging, we investigated the neural correlates of this behavioral effect. Developmental effects on correlations between brain activity and valuation parameters were obtained in regions that can be classified into (i) cognitive control regions, such as dorsolateral prefrontal cortex (DLPFC) and ventrolateral PFC; (ii) social cognition regions, such as posterior temporoparietal junction; and (iii) reward-related regions, such as ventromedial PFC (vmPFC) and ventral striatum. Within these regions, differential effects of advice on neural correlates of valuation were observed across development. Specifically, advice increased the correlation strength between brain activity and parameters reflective of safe choice options in adolescent DLPFC and decreased correlation strength between activity and parameters reflective of risky choice options in adult vmPFC. Taken together, results indicate that, across development, distinct brain systems involved in cognitive control and valuation mediate the risk-reducing effect of advice during decision making under risk via specific enhancements and reductions of the correlation strength between brain activity and valuation parameters.

Sacred values, such as those associated with religious or ethnic identity, underlie many important individual and group decisions in life, and individuals typically resist attempts to trade off their sacred values in exchange for material benefits. Deontological theory suggests that sacred values are processed based on rights and wrongs irrespective of outcomes, while utilitarian theory suggests that they are processed based on costs and benefits of potential outcomes, but which mode of processing an individual naturally uses is unknown. The study of decisions over sacred values is difficult because outcomes cannot typically be realized in a laboratory, and hence little is known about the neural representation and processing of sacred values. We used an experimental paradigm that used integrity as a proxy for sacredness and which paid real money to induce individuals to sell their personal values. Using functional magnetic resonance imaging (fMRI), we found that values that people refused to sell (sacred values) were associated with increased activity in the left temporoparietal junction and ventrolateral prefrontal cortex, regions previously associated with semantic rule retrieval. This suggests that sacred values affect behaviour through the retrieval and processing of deontic rules and not through a utilitarian evaluation of costs and benefits.

Although culture is usually thought of as the collection of knowledge and traditions that are transmitted outside of biology, evidence continues to accumulate showing how biology and culture are inseparably intertwined. Cultural conflict will occur only when the beliefs and traditions of one cultural group represent a challenge to individuals of another. Such a challenge will elicit brain processes involved in cognitive decision-making, emotional activation and physiological arousal associated with the outbreak, conduct and resolution of conflict. Key targets to understand bio-cultural differences include primitive drives-how the brain responds to likes and dislikes, how it discounts the future, and how this relates to reproductive behaviour-but also higher level functions, such as how the mind represents and values the surrounding physical and social environment. Future cultural wars, while they may bear familiar labels of religion and politics, will ultimately be fought over control of our biology and our environment.

Most decisions involve some element of uncertainty. When the outcomes of these decisions have different likelihoods of occurrence, the decision-maker must consider both the magnitude of each outcome and the probability of its occurrence, but how do individual decision makers combine the two dimensions of magnitude and probability? Here, we approach the problem by separating in time the presentation of magnitude and probability information, and focus the analysis of fMRI activations on the first piece of information only. Thus, we are able to identify distinct neural circuits for the two dimensions without the confounding effect of divided attention or the cognitive operation of combining them. We find that magnitude information correlates with the size of the response of the ventral striatum while probability information correlates with the response in the dorsal striatum. The relative responsiveness of these two striatal regions correlates with the behavioral tendency to weight one more than the other. The results are consistent with a second-order process of information aggregation in which individuals make separate judgments for magnitude and probability and then integrate those judgments., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The disposition effect is a phenomenon in which investors hold onto losing assets longer than they hold onto gaining assets. In this study, we used functional magnetic resonance imaging (fMRI) to measure the response of valuation regions in the brain during the decision to keep or to sell an asset that followed a random walk in price. The most common explanation for the disposition effect is preference-based: namely, that people are risk-averse over gains and risk-seeking over losses. This explanation would predict correlations between individuals' risk-preferences, the magnitude of their disposition effect, and activation in valuation structures of the brain. We did not observe these correlations. Nor did we find evidence for a realization utility explanation, which would predict differential responses in valuation regions during the decision to sell versus keep an asset that correlated with the magnitude of the disposition effect. Instead, we found an attenuated ventral striatum response to upticks in value below the purchase price in some individuals with a large disposition effect. Given the role of the striatum in signaling prediction error, the blunted striatal response is consistent with the expectation that an asset will rise when it is below the purchase price, thus spurring loss-holding behavior. This suggests that for some individuals, the disposition effect is likely driven by a belief that the asset will eventually return to the purchase price, also known as mean reversion., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Because of dogs' prolonged evolution with humans, many of the canine cognitive skills are thought to represent a selection of traits that make dogs particularly sensitive to human cues. But how does the dog mind actually work? To develop a methodology to answer this question, we trained two dogs to remain motionless for the duration required to collect quality fMRI images by using positive reinforcement without sedation or physical restraints. The task was designed to determine which brain circuits differentially respond to human hand signals denoting the presence or absence of a food reward. Head motion within trials was less than 1 mm. Consistent with prior reinforcement learning literature, we observed caudate activation in both dogs in response to the hand signal denoting reward versus no-reward.

The majority of decision-related research has focused on how the brain computes decisions over outcomes that are positive in expectation. However, much less is known about how the brain integrates information when all possible outcomes in a decision are negative. To study decision-making over negative outcomes, we used fMRI along with a task in which participants had to accept or reject 50/50 lotteries that could result in more or fewer electric shocks compared to a reference amount. We hypothesized that behaviorally, participants would treat fewer shocks from the reference amount as a gain, and more shocks from the reference amount as a loss. Furthermore, we hypothesized that this would be reflected by a greater BOLD response to the prospect of fewer shocks in regions typically associated with gain, including the ventral striatum and orbitofrontal cortex. The behavioral data suggest that participants in our study viewed all outcomes as losses, despite our attempt to induce a status quo. We find that the ventral striatum showed an increase in BOLD response to better potential gambles (i.e., fewer expected shocks). This lends evidence to the idea that the ventral striatum is not solely responsible for reward processing but that it might also signal the relative value of an expected outcome or action, regardless of whether the outcome is entirely appetitive or aversive. We also find a greater response to worse gambles in regions previously associated with aversive valuation, suggesting an opposing but simultaneous valuation signal to that conveyed by the striatum.

The application of neuroimaging methods to product marketing - neuromarketing - has recently gained considerable popularity. We propose that there are two main reasons for this trend. First, the possibility that neuroimaging will become cheaper and faster than other marketing methods; and second, the hope that neuroimaging will provide marketers with information that is not obtainable through conventional marketing methods. Although neuroimaging is unlikely to be cheaper than other tools in the near future, there is growing evidence that it may provide hidden information about the consumer experience. The most promising application of neuroimaging methods to marketing may come before a product is even released - when it is just an idea being developed.

It is well-known that social influences affect consumption decisions. We used functional magnetic resonance imaging (fMRI) to elucidate the neural mechanisms associated with social influence with regard to a common consumer good: music. Our study population was adolescents, age 12-17. Music is a common purchase in this age group, and it is widely believed that adolescent behavior is influenced by perceptions of popularity in their reference group. Using 15-s clips of songs from MySpace.com, we obtained behavioral measures of preferences and neurobiological responses to the songs. The data were gathered with, and without, the overall popularity of the song revealed. Song popularity had a significant effect on the participants' likability ratings of the songs. fMRI results showed a strong correlation between the participants' rating and activity in the caudate nucleus, a region previously implicated in reward-driven actions. The tendency to change one's evaluation of a song was positively correlated with activation in the anterior insula and anterior cingulate, two regions that are associated with physiological arousal and negative affective states. Sensitivity to popularity was linked to lower activation levels in the middle temporal gyrus, suggesting a lower depth of musical semantic processing. Our results suggest that a principal mechanism whereby popularity ratings affect consumer choice is through the anxiety generated by the mismatch between one's own preferences and others'. This mismatch anxiety motivates people to switch their choices in the direction of the consensus. Our data suggest that this is a major force behind the conformity observed in music tastes in some teenagers., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

Background: Myelination of white matter in the brain continues throughout adolescence and early adulthood. This cortical immaturity has been suggested as a potential cause of dangerous and impulsive behaviors in adolescence., Methodology/principal Findings: We tested this hypothesis in a group of healthy adolescents, age 12-18 (N = 91), who underwent diffusion tensor imaging (DTI) to delineate cortical white matter tracts. As a measure of real-world risk taking, participants completed the Adolescent Risk Questionnaire (ARQ) which measures engagement in dangerous activities. After adjusting for age-related changes in both DTI and ARQ, engagement in dangerous behaviors was found to be positively correlated with fractional anisotropy and negatively correlated with transverse diffusivity in frontal white matter tracts, indicative of increased myelination and/or density of fibers (ages 14-18, N = 60)., Conclusions/significance: The direction of correlation suggests that rather than having immature cortices, adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers.

Background: Financial advice from experts is commonly sought during times of uncertainty. While the field of neuroeconomics has made considerable progress in understanding the neurobiological basis of risky decision-making, the neural mechanisms through which external information, such as advice, is integrated during decision-making are poorly understood. In the current experiment, we investigated the neurobiological basis of the influence of expert advice on financial decisions under risk., Methodology/principal Findings: While undergoing fMRI scanning, participants made a series of financial choices between a certain payment and a lottery. Choices were made in two conditions: 1) advice from a financial expert about which choice to make was displayed (MES condition); and 2) no advice was displayed (NOM condition). Behavioral results showed a significant effect of expert advice. Specifically, probability weighting functions changed in the direction of the expert's advice. This was paralleled by neural activation patterns. Brain activations showing significant correlations with valuation (parametric modulation by value of lottery/sure win) were obtained in the absence of the expert's advice (NOM) in intraparietal sulcus, posterior cingulate cortex, cuneus, precuneus, inferior frontal gyrus and middle temporal gyrus. Notably, no significant correlations with value were obtained in the presence of advice (MES). These findings were corroborated by region of interest analyses. Neural equivalents of probability weighting functions showed significant flattening in the MES compared to the NOM condition in regions associated with probability weighting, including anterior cingulate cortex, dorsolateral PFC, thalamus, medial occipital gyrus and anterior insula. Finally, during the MES condition, significant activations in temporoparietal junction and medial PFC were obtained., Conclusions/significance: These results support the hypothesis that one effect of expert advice is to "offload" the calculation of value of decision options from the individual's brain.

While mainstream economic models assume that individuals treat probabilities objectively, many people tend to overestimate the likelihood of improbable events and underestimate the likelihood of probable events. However, a biological account for why probabilities would be treated this way does not yet exist. While undergoing fMRI, we presented individuals with a series of lotteries, defined by the voltage of an impending cutaneous electric shock and the probability with which the shock would be received. During the prospect phase, neural activity that tracked the probability of the expected outcome was observed in a circumscribed network of brain regions that included the anterior cingulate, visual, parietal, and temporal cortices. Most of these regions displayed responses to probabilities consistent with nonlinear probability weighting. The neural responses to passive lotteries predicted 79% of subsequent decisions when individuals were offered choices between different lotteries, and exceeded that predicted by behavior alone near the indifference point.

A decision maker may experience regret when a choice he makes results in a more adverse outcome than a different choice would have yielded. Analogously, he may experience rejoice when his choice resulted in better outcomes. We used fMRI to investigate the neural correlates of regret and rejoice where payoffs are in terms of a non-monetary medium. Incentives were created using painful outcomes in the form of mild electrical shocks to the foot and the possibility of avoiding them. We hypothesized that the neural response to a painful outcome resulting from an individual's choice would also reflect the degree of regret as measured by the likelihood that alternative choices would have yielded the same adverse outcome. Similarly, when an individual avoids a potential shock, he would experience a degree of rejoice that correlates with the probability he had of receiving the shock. For example, winning a bet when winning was unlikely, even if the outcome is the same, evokes more rejoice than winning when it was highly probable. Our results suggest that activation of a cortical network, consisting of the medial orbitofrontal cortex, left superior frontal cortex, right angular gyrus, and left thalamus, correlates with the degree of regret. A different network, including the rostral anterior cingulate, left hippocampus, left ventral striatum, and brain stem/midbrain correlated with rejoice. The right inferior orbitofrontal cortex, pre-supplementary motor area, anterior cingulate, and posterior cingulate showed similar patterns of activation with both regret and rejoice, suggesting that these regions may be associated with surprise from the realization of relatively unlikely events. Our results suggest that distinct, but overlapping networks are involved in the experiences of regret and rejoice.

Purpose: We summarize three previous neuroeconomic studies with two features that distinguish them from most others in experimental economics: (1) the use of physical pain to induce incentives and (2) acquisition of data on brain activation levels. By correlating behavior when payoffs are painful with brain activation, we are able to test for the neurobiological relevance of important phenomena previously observed in experimental studies that are at odds with classical economic theories of decision-making. These specific phenomena are (a) negative discounting of future payoffs; (b) nonlinear probability weighting; (c) the experience of regret and rejoice when making a decision under risk., Methodology/approach: The expectation of pain is created through the use of mild electric shocks to the top of the foot. Pain confers disutility, so decisions are made in the domain of losses relative to the status quo. Simultaneous with these decisions, brain activation data is acquired through functional magnetic resonance imaging (fMRI)., Findings: We find evidence for negative time discounting of electric shocks. Participants who exhibited the most extreme forms of this discounting were distinguished by early and robust activation of a subset of the cortical pain matrix. We also find evidence for probability weighting in the domain of electric shocks, which is manifest at the neural level. We find evidence both behaviorally and neurally for regret and rejoice functions for painful outcomes., Originality/value of Chapter: Previous experimental economic studies in the domain of losses have typically used monetary rewards. Here, we report behavioral effects and neural correlates using pain.

Interferon (IFN)-alpha is a cytokine of the innate immune response that is well known for inducing behavioral alterations and has been used to study effects of cytokines on the nervous system. Limited data, however, are available on the sites of action of IFN-alpha within the brain and their relationship with specific IFN-alpha-induced symptoms. Using a longitudinal design, whole-brain metabolic activity as assessed by fluorine-18-labeled fluorodeoxyglucose uptake and positron emission tomography was examined before and 4 weeks after IFN-alpha administration in patients with malignant melanoma. Changes in metabolic activity in relevant brain regions were then correlated with IFN-alpha-induced behavioral changes. IFN-alpha administration was associated with widespread bilateral increases in glucose metabolism in subcortical regions including the basal ganglia and cerebellum. Decreases in dorsal prefrontal cortex glucose metabolism were also observed. Prominent IFN-alpha-induced behavioral changes included lassitude, inability to feel, and fatigue. Correlational analyses revealed that self-reported fatigue (specifically as assessed by the 'energy' subscale of the Visual Analog Scale of Fatigue) was associated with increased glucose metabolism in the left nucleus accumbens and putamen. These data indicate that IFN-alpha as well as other cytokines of the innate immune response may target basal ganglia nuclei, thereby contributing to fatigue-related symptoms in medically ill patients.

Intertemporal choices are decisions with consequences that play out over time. These choices range from the prosaic--how much food to eat at a meal--to life-changing decisions about education, marriage, fertility, health behaviors and savings. Intertemporal preferences also affect policy debates about long-run challenges, such as global warming. Historically, it was assumed that delayed rewards were discounted at a constant rate over time. Recent theoretical and empirical advances from economic, psychological and neuroscience perspectives, however, have revealed a more complex account of how individuals make intertemporal decisions. We review and integrate these advances. We emphasize three different, occasionally competing, mechanisms that are implemented in the brain: representation, anticipation and self-control.

Modern economic theories of value derive from expected utility theory. Behavioral evidence points strongly toward departures from linear value weighting, which has given rise to alternative formulations that include prospect theory and rank-dependent utility theory. Many of the nonlinear forms for value assumed by these theories can be derived from the assumption that value is signaled by neurotransmitters in the brain, which obey simple laws of molecular movement. From the laws of mass action and receptor occupancy, we show how behaviorally observed forms of nonlinear value functions can arise.

Given the choice of waiting for an adverse outcome or getting it over with quickly, many people choose the latter. Theoretical models of decision-making have assumed that this occurs because there is a cost to waiting-i.e., dread. Using functional magnetic resonance imaging, we measured the neural responses to waiting for a cutaneous electric shock. Some individuals dreaded the outcome so much that, when given a choice, they preferred to receive more voltage rather than wait. Even when no decision was required, these extreme dreaders were distinguishable from those who dreaded mildly by the rate of increase of neural activity in the posterior elements of the cortical pain matrix. This suggests that dread derives, in part, from the attention devoted to the expected physical response and not simply from fear or anxiety. Although these differences were observed during a passive waiting procedure, they correlated with individual behavior in a subsequent choice paradigm, providing evidence for a neurobiological link between the experienced disutility of dread and subsequent decisions about unpleasant outcomes.