Clinical variables associated with major adverse cardiac events following radical cystectomy.

Objectives: The objective of this study is to investigate the association between major adverse cardiac events (MACE) and clinical factors of patients undergoing radical cystectomy (RC) for bladder cancer. Materials and Methods: A retrospective analysis using the 2015-2020 National Surgical Quality Improvement Program database was performed on patients who underwent RC for bladder cancer. MACE was defined as any report of cerebrovascular accident, myocardial infarction, or thromboembolic events (pulmonary embolism or deep vein thrombosis). A multivariable-adjusted logistic regression was conducted to identify clinical predictors of postoperative MACE. Results: A total of 10 308 (84.2%) patients underwent RC with incontinent urinary diversion (iUD), and 1938 (15.8%) underwent RC with continent urinary diversion (cUD). A total of 629 (5.1%) patients recorded a MACE, and on the multivariable-adjusted logistic regression, it was shown that MACE was significantly associated with increased age (OR = 1.035, 95% CI: 1.024-1.046, p < 0.001), obesity (OR = 1.583, 95% CI: 1.266-1.978, p < 0.001), current smokers (OR = 1.386, 95% CI: 1.130-1.700, p = 0.002), congestive heart failure before surgery (OR = 1.991, 95% CI: 1.016-3.900; p = 0.045), hypertension (OR = 1.209, 95% CI: 1.016-1.453, p = 0.043), and increase the surgical time (per 10 min increase, OR = 1.010, 95% CI: 1.003-1.017, p = 0.009). We also report that increased age, obesity, and patients undergoing cUD (OR = 1.368, 95% CI: 1.040-1.798; p = 0.025) are associated with thromboembolic events. Conclusion: By considering the preoperative characteristics of patients, including age, obesity, smoking, congestive heart failure, and hypertension status, urologists may be able to decrease the incidence of MACE in patients undergoing RC. Urologists should aim for lower operative times as this was associated with a decreased risk of thromboembolic events.

OpenMonkeyChallenge: Dataset and Benchmark Challenges for Pose Estimation of Non-human Primates.

The ability to automatically estimate the pose of non-human primates as they move through the world is important for several subfields in biology and biomedicine. Inspired by the recent success of computer vision models enabled by benchmark challenges (e.g., object detection), we propose a new benchmark challenge called OpenMonkeyChallenge that facilitates collective community efforts through an annual competition to build generalizable non-human primate pose estimation models. To host the benchmark challenge, we provide a new public dataset consisting of 111,529 annotated (17 body landmarks) photographs of non-human primates in naturalistic contexts obtained from various sources including the Internet, three National Primate Research Centers, and the Minnesota Zoo. Such annotated datasets will be used for the training and testing datasets to develop generalizable models with standardized evaluation metrics. We demonstrate the effectiveness of our dataset quantitatively by comparing it with existing datasets based on seven state-of-the-art pose estimation models.

Monkey visual attention does not fall into the uncanny valley.

Very humanlike artificial agents can induce feelings of uneasiness in human perceivers. Stimuli that generate this response are said to occupy "the uncanny valley". Given inconsistent findings in the literature, whether or not nonhuman animals experience the uncanny valley is unclear. Here, we recorded the visual attention of eleven male rhesus monkeys as they viewed faces varying in realness across five levels, with visual attention measured by both number and duration of visual fixations on faces as a whole and on areas of interest within the faces (e.g., eyes, mouth). Face stimuli varied in terms of the realism of the image and behavior depicted by the face (lipsmack, threat, bared teeth, and neutral). We largely found no support that rhesus monkeys perceive an uncanny valley when viewing our stimuli; however, monkeys did generally pay more attention to eyes and less attention to mouths in real images compared to less realistic images. Across all stimuli, monkeys' visual attention was drawn to the mouths of images when teeth were visible. These findings suggest that rhesus monkeys in our study did not display an uncanny valley effect when viewing realistic stimuli but did percieve affective information depicted by faces regardless of how real those faces appear.

Monkeys preferentially process body information while viewing affective displays.

Despite evolutionary claims about the function of facial behaviors across phylogeny, rarely are those hypotheses tested in a comparative context-that is, by evaluating how nonhuman animals process such behaviors. Further, while increasing evidence indicates that humans make meaning of faces by integrating contextual information, including that from the body, the extent to which nonhuman animals process contextual information during affective displays is unknown. In the present study, we evaluated the extent to which rhesus macaques (Macaca mulatta) process dynamic affective displays of conspecifics that included both facial and body behaviors. Contrary to hypotheses that they would preferentially attend to faces during affective displays, monkeys looked for longest, most frequently, and first at conspecifics' bodies rather than their heads. These findings indicate that macaques, like humans, attend to available contextual information during the processing of affective displays, and that the body may also be providing unique information about affective states. (PsycINFO Database Record

Network Patterns Associated with Navigation Behaviors Are Altered in Aged Nonhuman Primates.

The ability to navigate through space involves complex interactions between multiple brain systems. Although it is clear that spatial navigation is impaired during aging, the networks responsible for these altered behaviors are not well understood. Here, we used a within-subject design and [18F]FDG-microPET to capture whole-brain activation patterns in four distinct spatial behaviors from young and aged rhesus macaques: constrained space (CAGE), head-restrained passive locomotion (CHAIR), constrained locomotion in space (TREADMILL), and unconstrained locomotion (WALK). The results reveal consistent networks activated by these behavior conditions that were similar across age. For the young animals, however, the coactivity patterns were distinct between conditions, whereas older animals tended to engage the same networks in each condition. The combined observations of less differentiated networks between distinct behaviors and alterations in functional connections between targeted regions in aging suggest changes in network dynamics as one source of age-related deficits in spatial cognition. SIGNIFICANCE STATEMENT: We report how whole-brain networks are involved in spatial navigation behaviors and how normal aging alters these network patterns in nonhuman primates. This is the first study to examine whole-brain network activity in young or old nonhuman primates while they actively or passively traversed an environment. The strength of this study resides in our ability to identify and differentiate whole-brain networks associated with specific navigational behaviors within the same nonhuman primate and to compare how these networks change with age. The use of high-resolution PET (microPET) to capture brain activity of real-world behaviors adds significantly to our understanding of how active circuits critical for navigation are affected by aging.

The Rhesus Monkey Connectome Predicts Disrupted Functional Networks Resulting from Pharmacogenetic Inactivation of the Amygdala.

Contemporary research suggests that the mammalian brain is a complex system, implying that damage to even a single functional area could have widespread consequences across the system. To test this hypothesis, we pharmacogenetically inactivated the rhesus monkey amygdala, a subcortical region with distributed and well-defined cortical connectivity. We then examined the impact of that perturbation on global network organization using resting-state functional connectivity MRI. Amygdala inactivation disrupted amygdalocortical communication and distributed corticocortical coupling across multiple functional brain systems. Altered coupling was explained using a graph-based analysis of experimentally established structural connectivity to simulate disconnection of the amygdala. Communication capacity via monosynaptic and polysynaptic pathways, in aggregate, largely accounted for the correlational structure of endogenous brain activity and many of the non-local changes that resulted from amygdala inactivation. These results highlight the structural basis of distributed neural activity and suggest a strategy for linking focal neuropathology to remote neurophysiological changes.

Maternal immune activation in nonhuman primates alters social attention in juvenile offspring.

BACKGROUND: Sickness during pregnancy is associated with an increased risk of offspring neurodevelopmental disorders. Rodent models have played a critical role in establishing causal relationships and identifying mechanisms of altered brain and behavior development in pups prenatally exposed to maternal immune activation (MIA). We recently developed a novel nonhuman primate model to bridge the gap between human epidemiological studies and rodent models of prenatal immune challenge. Our initial results demonstrated that rhesus monkeys given the viral mimic synthetic double-stranded RNA (polyinosinic:polycytidylic acid stabilized with poly-l-lysine) during pregnancy produce offspring with abnormal repetitive behaviors, altered communication, and atypical social interactions. METHODS: We utilized noninvasive infrared eye tracking to further evaluate social processing capabilities in a subset of the first trimester MIA-exposed offspring (n = 4) and control animals (n = 4) from our previous study. RESULTS: As juveniles, the MIA offspring differed from control animals on several measures of social attention, particularly when viewing macaque faces depicting the fear grimace facial expression. Compared with control animals, MIA offspring had a longer latency before fixating on the eyes, had fewer fixations directed at the eyes, and spent less total time fixating on the eyes of the fear grimace images. CONCLUSIONS: In the rhesus monkey model, exposure to MIA at the end of the first trimester results in abnormal gaze patterns to salient social information. The use of noninvasive eye tracking extends the findings from rodent MIA models to more human-like behaviors resembling those in both autism spectrum disorder and schizophrenia.

Macaque cardiac physiology is sensitive to the valence of passively viewed sensory stimuli.

Autonomic nervous system activity is an important component of affective experience. We demonstrate in the rhesus monkey that both the sympathetic and parasympathetic branches of the autonomic nervous system respond differentially to the affective valence of passively viewed video stimuli. We recorded cardiac impedance and an electrocardiogram while adult macaques watched a series of 300 30-second videos that varied in their affective content. We found that sympathetic activity (as measured by cardiac pre-ejection period) increased and parasympathetic activity (as measured by respiratory sinus arrhythmia) decreased as video content changes from positive to negative. These findings parallel the relationship between autonomic nervous system responsivity and valence of stimuli in humans. Given the relationship between human cardiac physiology and affective processing, these findings suggest that macaque cardiac physiology may be an index of affect in nonverbal animals.

Pervasive alterations of emotional and neuroendocrine responses to an acute stressor after neonatal amygdala lesions in rhesus monkeys.

The current study examined the long-term effects of neonatal amygdala lesions on emotional and hypothalamic-pituitary-adrenal (HPA) axis reactivity to an acute stressor in rhesus monkeys. Rhesus monkeys received either bilateral MRI-guided ibotenic acid amygdala (Neo-Aibo; n=6) or sham (Neo-C; n=7) lesions between 7 and 14 days of age. Emotional reactivity was assessed using the Human Intruder paradigm at 2 months, 4.5 months, and 6-8 years of age, whereas stress neuroendocrine response was only assessed in adulthood (6-8 years). The modulation of defensive and emotional behaviors based on the gaze direction of the intruder emerged between 2 and 4 months of age in surrogate-peer reared sham-operated infant monkeys, as already shown for mother-reared infants. Although neonatal amygdala lesions did not impair the ability to exhibit defensive and emotional behaviors, it altered the modulation of these responses based on the intruder's gaze direction. The changes in emotional reactivity after neonatal amygdala lesions emerged in infancy and persisted throughout adulthood when they were associated with a reduction of basal cortisol levels and a blunted cortisol response to the stressor. These changes are reminiscent of those found after adult-onset amygdala lesions, demonstrating little functional compensation following early amygdala damage.

Behavioral outcomes of late-onset or early-onset orbital frontal cortex (areas 11/13) lesions in rhesus monkeys.

The orbital frontal cortex (OFC) has been implicated in a number of psychiatric disorders, including depression, anxiety, phobia, and obsessive-compulsive disorder. Thus, a better understanding of its functions will likely provide critical information to understand the specific behavioral and cognitive processes affected in these human disorders. In recent years, a growing number of studies have provided evidence for anatomical and functional differentiation within the OFC. Here we discuss the effects of selective OFC (areas 11/13) lesions on social behavior, emotional regulation, and behavioral adaptation. Damage to these specific OFC subfields in adult monkeys resulted in profound changes in the flexible modulation of responses guided by reward value that could explain the poor fear regulation and disturbed social interactions observed in the same animals. A similar pattern of results was found when the OFC lesions were done in infancy. Thus, in monkeys, self-regulation abilities mediated by OFC areas 11/13 emerge from midinfancy through adolescence.

Social and nonsocial content differentially modulates visual attention and autonomic arousal in Rhesus macaques.

The sophisticated analysis of gestures and vocalizations, including assessment of their emotional valence, helps group-living primates efficiently navigate their social environment. Deficits in social information processing and emotion regulation are important components of many human psychiatric illnesses, such as autism, schizophrenia and social anxiety disorder. Analyzing the neurobiology of social information processing and emotion regulation requires a multidisciplinary approach that benefits from comparative studies of humans and animal models. However, many questions remain regarding the relationship between visual attention and arousal while processing social stimuli. Using noninvasive infrared eye-tracking methods, we measured the visual social attention and physiological arousal (pupil diameter) of adult male rhesus monkeys (Macaca mulatta) as they watched social and nonsocial videos. We found that social videos, as compared to nonsocial videos, captured more visual attention, especially if the social signals depicted in the videos were directed towards the subject. Subject-directed social cues and nonsocial nature documentary footage, compared to videos showing conspecifics engaging in naturalistic social interactions, generated larger pupil diameters (indicating heightened sympathetic arousal). These findings indicate that rhesus monkeys will actively engage in watching videos of various kinds. Moreover, infrared eye tracking technology provides a mechanism for sensitively gauging the social interest of presented stimuli. Adult male rhesus monkeys' visual attention and physiological arousal do not always trend in the same direction, and are likely influenced by the content and novelty of a particular visual stimulus. This experiment creates a strong foundation for future experiments that will examine the neural network responsible for social information processing in nonhuman primates. Such studies may provide valuable information relevant to interpreting the neural deficits underlying human psychiatric illnesses such as autism, schizophrenia and social anxiety disorder.

Eye-tracking with nonhuman primates is now more accessible than ever before.

Human and nonhuman primates rely almost exclusively on vision for social communication. Therefore, tracking eye movements and examining visual scan paths can provide a wealth of information about many aspects of primate social information processing. Although eye-tracking techniques have been utilized with humans for some time, similar studies in nonhuman primates have been less frequent over recent decades. This has largely been owing to the need for invasive manipulations, such as the surgical implantation of devices to limit head movement, which may not be possible in some laboratories or at some universities, or may not be congruent with some experimental aims (i.e., longitudinal studies). It is important for all nonhuman primate researchers interested in visual information processing or operant behavior to realize that such invasive procedures are no longer necessary. Here, we briefly describe new methods for fully noninvasive video eye-tracking with adult rhesus monkeys (Macaca mulatta). We also describe training protocols that require only ∼30 days to accomplish and quality control measures that promote reliable data collection. It is our hope that this brief overview will reacquaint nonhuman primate researchers with the benefits of eye-tracking and promote expanded use of this powerful methodology.

Selective changes in foraging behavior following bilateral neurotoxic amygdala lesions in rhesus monkeys.

Across a variety of species, the amygdala appears to play a key role in the detection and avoidance of potential dangers (e.g., unfamiliar social partners, novel objects or contexts, potential predators, etc.). For many species, seeking out appropriate food sources and avoiding novel, distasteful or potentially tainted food is also a daily concern. Amygdala damage in nonhuman primates has been linked to increased willingness to select unfamiliar or unpalatable foods, as well as inedible items that intact animals typically reject. However, such findings have not always been consistent and have typically been observed in relatively restrictive, laboratory-based testing contexts. We evaluated the food choices of six adult male rhesus monkeys (Macaca mulatta) with bilateral, neurotoxic amygdala lesions and six age- and experienced-matched unoperated control animals. Each animal was able to forage freely in a large enclosure stocked with five preferred and five nonpreferred foods that changed locations each day. While both groups quickly selected palatable foods, monkeys with amygdala lesions consistently selected unpalatable foods that the unoperated control animals generally avoided. Even after repeated presentations of the unpalatable foods, the amygdala-lesioned monkeys failed to change their initial pattern of diminished avoidance. These results are consistent with a general role for the amygdala in danger detection and prevention of harm in the presence of novel or noxious stimuli, regardless of whether such stimuli are conspecifics, predators, objects or foods.

Maturation of the hippocampal formation and amygdala in Macaca mulatta: a volumetric magnetic resonance imaging study.

Malformations of the hippocampal formation and amygdala have been implicated in several neurodevelopmental disorders; yet relatively little is known about their normal structural development. The purpose of this study was to characterize the early developmental trajectories of the hippocampus and amygdala in the rhesus macaques (Macaca mulatta) using noninvasive MRI techniques. T1-weighted structural scans of 22 infant and juvenile monkeys (11 male, 11 female) were obtained between 1 week and approximately 2 yrs of age. Ten animals (five males, five females) were scanned multiple times and 12 monkeys (six males, six females) were scanned once between 1 and 4 weeks of age. Both structures exhibited significant age-related changes throughout the first 2 yrs of life that were not explained by overall brain development. The hippocampal formation increased 117.05% in males and 110.86% in females. No sex differences were evident, but the left hemisphere was significantly larger than the right. The amygdala increased 86.49% in males and 72.94% in females with males exhibiting a larger right than left amygdala. For both structures, the most substantial volumetric increases were seen within the first month, but the hippocampal formation appeared to develop more slowly than the amygdala with the rate of hippocampal maturation stabilizing around 11 months and that of amygdala maturation stabilizing around 8 months. Differences in volumetric developmental trajectories of the hippocampal formation and amygdala largely mirror differences in the timing of the functional development of these structures. The current results emphasize the importance of including early postnatal ages when assessing developmental trajectories of neuroanatomical structures and reinforces the utility of nonhuman primates in the assessment of normal developmental patterns.

Impact of amygdala, orbital frontal, or hippocampal lesions on threat avoidance and emotional reactivity in nonhuman primates.

The authors measured the effects of bilateral amygdaloid, orbital frontal, or hippocampal lesions on emotional reactivity and passive avoidance in rhesus monkeys (Macaca mulatta). Animals were presented with 8 neutral or 8 aversive objects, each paired with a highly preferred food reward. Sham-operated control animals displayed heightened defensive behaviors and typically would not approach or retrieve the food when paired with a potential predator (coiled rubber snake), 2 conditioned aversive stimuli for laboratory-housed monkeys (a capture net and leather handling gloves), and 1 object displaying a threatening social signal (direct eye contact from a human-like doll). Animals with amygdala lesions, but not hippocampal or orbital frontal lesions, showed less tension-related behaviors and diminished passive avoidance of the rubber snake and its matched neutral item (a coiled piece of hose) relative to control animals. All operated groups displayed normal patterns of behavior toward conditioned and socially aversive objects. These results expand our understanding of how the primate brain evaluates reward and threat, and indicate a highly specialized role for the amygdala in mediating passive avoidance and emotional reactivity to potentially life-threatening stimuli.

Behavioral and hormonal reactivity to threat: effects of selective amygdala, hippocampal or orbital frontal lesions in monkeys.

We compared the effects of bilateral amygdala, hippocampal or orbital frontal cortex lesions on emotional and hormonal reactivity in rhesus monkeys (Macaca mulatta). Experiment 1 measured behavioral reactivity to an unfamiliar human intruder before and after surgery. Animals with amygdala lesions demonstrated decreases in one passive defensive behavior (freezing), whereas animals with hippocampal lesions showed decreases in a more stimulus-directed defensive behavior (tooth grinding). Orbital frontal cortex lesions also reduced these two defensive behaviors, as well as decreased cage-shaking dominance displays. Animals with amygdala, hippocampal or sham lesions also demonstrated increased tension-related behaviors after surgery, but those with orbital frontal lesions did not. Finally, all three lesions diminished the operated animals' ability to modulate tension-related behaviors depending on the magnitude of threat posed by the human intruder. Experiment 2 measured circulating levels of cortisol and testosterone when a subset of these same animals was at rest and following physical restraint, temporary isolation, exposure to threatening objects and social interactions with an unfamiliar conspecific. None of the lesions impacted on testosterone levels in any condition. Amygdala or orbital frontal lesions blunted cortisol reactivity during isolation from peers, but not during any other condition. Hippocampal lesions did not alter circulating levels of cortisol under any condition. These results indicate that the amygdala, hippocampus and orbital frontal cortex play distinct, yet complimentary roles in coordinating emotional and hormonal reactivity to threat.

Bilateral neurotoxic amygdala lesions in rhesus monkeys (Macaca mulatta): consistent pattern of behavior across different social contexts.

Although the amygdala has been repeatedly implicated in normal primate social behavior, great variability exists in the specific social and nonsocial behavioral changes observed in nonhuman primates with bilateral amygdala lesions. One plausible explanation pertains to differences in social context. This study measured the social behavior of amygdala-lesioned and unoperated rhesus monkeys (Macaca mulatta) in 2 contexts. Monkeys interacted in 4-member social groups over 32 test days. They were previously assessed in pairs (N. J. Emery et al., 2001) and were therefore familiar with each other at the beginning of this study. Across the 2 contexts, amygdala lesions produced a highly consistent pattern of social behavior. Operated monkeys engaged in more affiliative social interactions with control partners than did controls. In the course of their interactions, amygdala-lesioned monkeys also displayed an earlier decrease in nervous and fearful personality qualities than did controls. The increased exploration and sexual behavior recorded for amygdala-lesioned monkeys in pairs was not found in the 4-member groups. The authors concluded that the amygdala contributes to social inhibition and that this function transcends various social contexts.

Effects of neonatal amygdala or hippocampus lesions on resting brain metabolism in the macaque monkey: a microPET imaging study.

Longitudinal analysis of animals with neonatal brain lesions enables the evaluation of behavioral changes during multiple stages of development. Interpretation of such changes, however, carries the caveat that permanent neural injury also yields morphological and neurochemical reorganization elsewhere in the brain that may lead either to functional compensation or to exacerbation of behavioral alterations. We have measured the long-term effects of selective neonatal brain damage on resting cerebral glucose metabolism in nonhuman primates. Sixteen rhesus monkeys (Macaca mulatta) received neurotoxic lesions of either the amygdala (n=8) or hippocampus (n=8) when they were two weeks old. Four years later, these animals, along with age- and experience-matched sham-operated control animals (n=8), were studied with high-resolution positron emission tomography (microPET) and 2-deoxy-2[(18)F]fluoro-d-glucose ([(18)F]FDG) to detect areas of altered metabolism. The groups were compared using an anatomically-based region of interest analysis. Relative to controls, amygdala-lesioned animals displayed hypometabolism in three frontal lobe regions, as well as in the neostriatum and hippocampus. Hypermetabolism was also evident in the cerebellum of amygdala-lesioned animals. Hippocampal-lesioned animals only showed hypometabolism in the retrosplenial cortex. These results indicate that neonatal amygdala and hippocampus lesions induce very different patterns of long-lasting metabolic changes in distant brain regions. These observations raise the possibility that behavioral alterations in animals with neonatal lesions may be due to the intended damage, to consequent brain reorganization or to a combination of both factors.

The effects of selective amygdala, orbital frontal cortex or hippocampal formation lesions on reward assessment in nonhuman primates.

We examined the effects of bilateral amygdaloid, hippocampal or orbital frontal cortex lesions on reward assessment in rhesus monkeys (Macaca mulatta). In Experiment 1, basic preferences for foods and inedible nonfoods were measured pre- and postsurgery. None of the lesions produced changes in animals' preferences for palatable foods or raw meat relative to presurgery, although amygdaloid or hippocampal lesions yielded increased preference for inedible nonfoods postsurgery. When the reinforcement value of each animal's highest-preferred food was decreased by selective satiation, only animals with neurotoxic orbital frontal cortex lesions continued to select the sated food. Experiment 2 measured the impact of each lesion on learning 60 concurrent discrimination problems and, then, on flexibly avoiding objects associated with sated foods in favour of objects associated with nonsated foods. None of the lesions affected concurrent discrimination learning, but animals with neurotoxic amygdala or aspiration orbital frontal lesions could not refrain from displacing items covering devalued foods. Only animals with orbital lesions also selected the devalued food beneath the object. The results indicate a functional dissociation for the amygdala and orbital frontal cortex in reward assessment, depending on the type of the reinforcer available (objects vs. food). Finally, this is the first study indicating that the hippocampal formation is involved in the assessment of familiar nonfoods, but not in judging the current value of unconditioned and conditioned reinforcers.

The impact of selective amygdala, orbital frontal cortex, or hippocampal formation lesions on established social relationships in rhesus monkeys (Macaca mulatta).

Social dominance, personality ratings, and frequency, duration, and timing of social behaviors were measured pre- and postsurgically in 6 groups of rhesus monkeys (Macaca mulatta), each consisting of 1 sham-operated control and 1 monkey each with a selective amygdala, hippocampal, or orbital frontal cortex lesion. Unlike previous reports, none of the operated groups showed changes in social dominance postsurgery, although changes in other measures varied by lesion site. Although sham-operated monkeys displayed heightened avoidant, anxious, and aggressive behaviors, those with hippocampal lesions also showed increased exploration and excitability, along with reduced responses to affiliative signals. Amygdala lesions yielded several personality changes that precluded positive social interactions (increased exploration and excitability, decreased affiliation and popularity) and altered responses to threatening social signals. By contrast, monkeys with orbital frontal lesions were involved in more aggressive interactions and responded differently to both affiliative and threatening signals. Although several findings differ from earlier nonhuman primate studies, they are largely in agreement with human data and emphasize the context-specific nature of social behavior studies. Interpretation of results in relation to cognitive processes mediated by each structure is discussed.