Value judgments and self-control of action: The role of the medial frontal cortex

Humans generate actions in relation to perceived events in the environment. Events are valuated in terms of subjective (personal) relevance or meaning, i.e. “what does this mean to me?”. Similarly, making sense or gaining meaning from sensations (i.e., “perception”) from one's own body and of mental images, such as memories or intentions, involves valuation from a subjective perspective. Here, we review recent findings in neurophysiology and neuroimaging suggesting that the medial frontal cortex comprises cortical relay nodes that afford the attribution of self-relevant, immediate and intuitive (implicit) meaning. In addition, we describe recent data that suggest that the medial frontal cortex participates also in the explicit appraisal of certain stimuli, namely, emotional face expressions, occurring as early as 150 ms following the stimulus. We propose that the medial frontal cortex subserves egocentric “value” judgments (both implicit and explicit), which are critical for self-control of action.     

Types of memory or attention? Impairments after lesions of the hippocampus and limbic ventral tegmentum

An animal with an unimpaired “reference” memory can distinguish between alternatives that belong to a rewarded set and those that are unrewarded. An animal with an unimpaired “working” memory can distinguish between alternatives where it has been rewarded (e.g., food has been eaten and not replaced) and those where it will be rewarded. Olton et al. [19] proposed that rats with fimbria-fornix or hippocampal damage showed a lasting deficit specific to “working” memory. This hypothesis has been tested for animals with damage to the hippocampus, limbic ventral tegmentum, neocortex and for intact and operated controls on a task where food pellets must be found in four of 16 holes in a “hole-board” arena. Only the first two groups were impaired in acquiring this task. The impairment was marked for both types of “memory.” It is proposed that the deficit may, in part, be accounted for by deficits in the selective mechanisms related to attention.     

Functional significance of the rapid regulation of brain estrogen action: where do the estrogens come from?

Estrogens exert a wide variety of actions on reproductive and non-reproductive functions. These effects are mediated by slow and long lasting genomic as well as rapid and transient non-genomic mechanisms. Besides the host of studies demonstrating the role of genomic actions at the physiological and behavioral level, mounting evidence highlights the functional significance of non-genomic effects. However, the source of the rapid changes in estrogen availability that are necessary to sustain their fast actions is rarely questioned. For example, the rise of plasma estrogens at pro-estrus that represents one of the fastest documented changes in plasma estrogen concentration appears too slow to explain these actions. Alternatively, estrogen can be synthesized in the brain by the enzyme aromatase providing a source of locally high concentrations of the steroid. Furthermore, recent studies demonstrate that brain aromatase can be rapidly modulated by afferent inputs, including glutamatergic afferents. A role for rapid changes in estrogen production in the central nervous system is supported by experiments showing that acute aromatase inhibition affects nociception as well as male sexual behavior and that preoptic aromatase activity is rapidly (within min) modulated following mating. Such mechanisms thus fulfill the gap existing between the fast actions of estrogen and their mode of production and open new avenues for the understanding of estrogenic effects on the brain.     

Pharmacological inhibition of mitochondrial membrane permeabilization for neuroprotection

Recent data have provided important clues about the molecular mechanisms underlying certain neurodegenerative diseases. Most cell death in vertebrates proceeds via the mitochondrial pathway of apoptosis. Mitochondria contain proapoptotic factors such as cytochrome c and AIF in their intermembrane space. Furthermore, mitochondrial membrane permeabilization (MMP) is a critical event during apoptosis, representing the “point of no return” of the lethal process. Modern medicine is developing an increasing number of drugs for neurodegenerative disease, but no neuroprotective treatment has yet been established. While current treatments temporarily alleviate symptoms, they do not halt disease progression. This paper briefly reviews the pharmacological inhibition of mitochondrial membrane permeabilization for neuroprotection.     

Novel mechanisms for neuroendocrine regulation of aggression

In 1849, Berthold demonstrated that testicular secretions are necessary for aggressive behavior in roosters. Since then, research on the neuroendocrinology of aggression has been dominated by the paradigm that the brain receives gonadal hormones, primarily testosterone, which modulate relevant neural circuits. While this paradigm has been extremely useful, recent studies reveal important alternatives. For example, most vertebrate species are seasonal breeders, and many species show aggression outside of the breeding season, when gonads are regressed and circulating testosterone levels are typically low. Studies in birds and mammals suggest that an adrenal androgen precursor—dehydroepiandrosterone (DHEA)—may be important for the expression of aggression when gonadal testosterone synthesis is low. Circulating DHEA can be metabolized into active sex steroids within the brain. Another possibility is that the brain can autonomously synthesize sex steroids de novo from cholesterol, thereby uncoupling brain steroid levels from circulating steroid levels. These alternative neuroendocrine mechanisms to provide sex steroids to specific neural circuits may have evolved to avoid the “costs” of high circulating testosterone during particular seasons. Physiological indicators of season (e.g., melatonin) may allow animals to switch from one neuroendocrine mechanism to another across the year. Such mechanisms may be important for the control of aggression in many vertebrate species, including humans.     

The functional significance of mu rhythms: Translating “seeing” and “hearing” into “doing”

Existing evidence indicates that mu and other alpha-like rhythms are independent phenomena because of differences in source generation, sensitivity to sensory events, bilateral coherence, frequency, and power. Although mu suppression and enhancement echo sensorimotor processing in frontoparietal networks, they are also sensitive to cognitive and affective influences and likely reflect more than an idling brain state. Mu rhythms are present at early stages of human development and in other mammalian species. They exhibit adaptive and dynamically changing properties, including frequency acceleration and posterior-to-anterior shifts in focus. Furthermore, individuals can learn to control mu rhythms volitionally in a very short period of time. This raises questions about the mu rhythm's open neural architecture and ability to respond to cognitive, affective, and motor imagery, implying an even greater developmental and functional role than has previously been ascribed to it. Recent studies have suggested that mu rhythms reflect downstream modulation of motor cortex by prefrontal mirror neurons, i.e., cells that may play a critical role in imitation learning and the ability to understand the actions of others. It is proposed that mu rhythms represent an important information processing function that links perception and action—specifically, the transformation of “seeing” and “hearing” into “doing.” In a broader context, this transformation function results from an entrainment/gating mechanism in which multiple alpha networks (visual-, auditory-, and somatosensory-centered domains), typically producing rhythmic oscillations in a locally independent manner, become coupled and entrained. A global or ‘diffuse and distributed alpha system’ comes into existence when these independent sources of alpha become coherently engaged in transforming perception to action.     

On the possible functional role of afferent pathways in skin sensation

Single unit activity was recorded from postcentral gyrus (SI) neurons in chronically prepared macaque monkeys. Lesions of the dorsal funiculi (especially cuneatus), or the lateral lemniscus (at the mesencephalic level) failed to significantly modify the properties of the cortical responses to peripheral stimuli, while combined lesions of both pathways were quite effective in this regard. An additional finding was that combined “deafferentation” of a hemisphere caused a significant proportion of cells in it to respond to ipsilateral stimuli. We conclude that both the medial lemniscal and spinothalamic pathways carry information—in parallel—to the cortex, that this information is conveyed in two modes by each pathway (“elemental” and “convergent”) and that ipsilateral inputs relayed to SI are revealed by partial deafferentation of its contralateral inputs.     

Evaluation of two automated metrics for analyzing partner preference tests

The partner preference test (PPT) is commonly used to examine sexual and social preferences in rodents. The test offers experimental subjects a choice between two stimulus animals, and time spent with each is used to calculate a preference score. In monogamous prairie voles (Microtus ochrogaster), the PPT has been paramount to the study of pair bonding. Although powerful, use of the PPT in voles has depended primarily on human manual scoring. Manual scoring is time-consuming and is susceptible to bias and fatigue, limiting the use of the PPT in high-throughput studies. Here we compared manual scoring (real-time and 16×) and two automated scoring metrics: “social proximity” and “immobile social contact”. We hypothesized that “immobile social contact” would provide data most comparable to manually scored “huddling”, and thus be the most sensitive measure of partner preference in prairie voles. Each automated metric produced data that highly correlated with manual scoring (R > 0.90); however, “immobile social contact” more closely reflected manually scored huddling (R = 0.99; P < 0.001). “Social proximity” and “immobile social contact” were then used to detect group partner preferences in four data sets that varied by cohabitation length and sex. “Immobile social contact” revealed a significant partner preference in each data set; “social proximity” detected partner preferences in only three of the four. Our results demonstrate the utility of automated systems in high-throughput PPTs, and further confirm that automated systems capable of scoring “immobile social contact” yield results indistinguishable from manual scoring.     

Project reachout: Building social skills through art and video

A group of nine “educationally unserved” adolescents (categorically defined by PL 94-142 or “drop outs” as defined by the Providence School Department) underwent an innovative combination of treatments—art therapy, social skills training and video therapy. The outcome suggests that the combination significantly elevates feelings of self worth and esteem in the students and that such feelings are also perceived by teachers and other independent observers.