User:Niubrad
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Phoenix Bradley Monakhos. I'm a neurobiology grad student at San Diego State University. I am currently doing research with mirror neurons, using functional MRI scanning techniques. I also work in a teratology lab where we look for treatments for fetal alcohol spectrum disorders.
Wikipedia is my friend.
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CURRICULUM VITAE
Graduate Assistant SDSU Behavioral Neurobiology and Teratology Lab San Diego State University
Degrees
Ph.D. Neuroscience in progress B.S. Biology B.A. Psychology
Techniques & Experience
Techniques for Brain Imaging Certified G.E. fMRI scanning technician, functional and DTI experience, Psyscope-presentation, AFNI, X11 Darwin, Terminal, RSF-Gen, Matlab
Techniques for Behavioral Neurobiology Autoradiography, in situ hybridization, thin layer chromatography, histology, electromyography biofeedback, perfusion, rodent surgery, chemicals preparation, behavioral testing of various paradigms, ImageQuant, Optical Defractionator, basic computer programming, experimental design, statistical analysis using Excel and SPSS, intubation and injection in rodents, blood alcohol analysis, tissue embedding, vapor inhalation ethanol exposure modeling
Article I wrote about the benefits, practicality, and caveats of using single neuron groups to explain specific behaviors.
Introduction
Over the past century scientists have made significant progress in developing theories of why humans think, act, and feel the way they do. Our understanding of behavior and cognition can be thought of as series of discoveries that have helped to bridge the gap between what we know, what we predict, and what we observe. While psychology has origins dating back to ancient Greece, neuroscience is a relatively new discipline. This can be partially attributed to the complex nature of the human mind, and until recently the physical apparatus of the brain was largely excluded from texts equating behavior and cognition. The separation between mind and body would not remain, and as new discoveries surfaced, the need for psychologists to be well versed in the hard sciences, such as biology, has never been more essential. Neuroscience has laid the foundation for a new paradigm of psychology that has adopted the arduous task of explaining the complexities of the human brain. Aided by advanced technology, neuroscientists are now able to “look” inside the brains of living organisms (including humans) while they think and act just as they would in everyday life. So what was once considered an extraordinary pursuit is now being pushed farther than one could have ever anticipated only 20 years ago. Due to the inherent wonder humans have for their own mind, a series of paradoxes follow. Douglass Adams uses this bit of satire in his comedy, A Hitchhikers Guide to the Galaxy to attack the vices and follies of humankind's struggle to find the answer "…to life, the universe, and everything." In Adams novel, after a computer designed by human-like beings returns the answer to this question as the numerical value 42, sentient beings are faced with the even more perplexing task of finding the ultimate question. Thus, even with an unlimited budget and armed with an arsenal of cutting edge technology, brain science can only advance as far and as fast as the incitefullness of the questions asked by it's underwriters. How ironic are the matters of neuroscientists; learning about learning, trying to understand how we understand, and using the brain to ask questions about the brain. Now that we have the technology to "look," we face that exhausting question: what should we want to find? In my mind this issue may be channeled best through a sequent rationalization, connecting big to small, complex to simple, diversity to similarity, and phenomena to epiphenomena. One can find extraordinary diversity in the experiences in which they partake; on the other hand, the people whom they encounter are remarkably similar. They are curious; they strive for love and acceptance, and feel pain when removed from such necessities. They look after one another, and have a strong devotion to justice. Yet, they will also do harm for power and resources, and discriminate against others that belong to a group with whom they do not identify themselves. So the major question I ask myself is: what makes individuals so similar, yet display such variability in their actions. When considering this topic of understanding, I feel it is important to start small, simple, and similar, and then build the theoretical framework from these principles. The following review will cover two fairly new discoveries in the world of neuroscience; mirror neurons and spatial neurons. I've chosen these two neurological entities (NEs) because they might prove to be the fundamental microstructures responsible for an array of complex behavior. It is my hope that studying these structures will provide an example of the gradual advancement from tangible entities and quantifiable processes to the ethereal phenomena and convoluted behavior manifested socially by humans, nonetheless explained by basic scientific methods. Along with defining the anatomy and function of these two NEs, the text will cite examples of cases where these structures become damaged or disabled, in order to give the reader a broader scope of how they work. Note that the common thread between these two NEs is their ability to account for specific behavioral phenomena on a cellular level, which is a concept that has been met with both inquiry and reservation in certain academic circles. Some researchers have qualms (many of them justified) about the precise nature of explaining the complexities of behavior with such a reductionist approach. Therefore, I will address these concerns the best I can. Nevertheless, this essay should pose an exciting question for future research; can we understand behavior by studying individual neurons?
The Mirror Neuron System Mirror neurons were first discovered in area F5 of the macaque monkey premotor cortex in a somewhat serendipitous fashion. DiPellegrino (1992) quite candidly sums up the unexpected findings in his write-up about the experiment, which took place in the Rizzolatti lab in Parma, Italy:
Our original aim in the present experiment was to study the activity of F5 neurons in a behavioral situation in which we could separate stimulus-associated responses from the activity related to movements. For this purpose a macaque monkey was trained to retrieve objects of different size and shape from a testing box with a variable delay after a stimulus presentation. After the initial recording experiments, we incidentally observed that some of the experimenter’s actions, such as picking up the food or placing it inside the testing box, activated a relatively large proportion of F5 neurons in the absence of any overt movement of the monkey. The purpose of this communication is to describe some of the essential features of this surprising new class of premotor neurons.
What they had found was a link between an executed behavior and the ability to recognize the identical behavior performed by another individual. More precisely, specific neuronal excitations were recorded by an implanted microelectrode when a monkey performed a particular action (i.e. reaching to grab a peanut); the very same neuron would excite the electrode when the monkey observed the same action performed by another individual (DiPellegrino et al.1992). Since the initial discovery of these visuomotor F5 neurons, much work has been done in order to elucidate their specific properties. Two types of visuomotor neurons, canonical and mirror, have been defined by Rizzolatti and Luppino (2001). Canonical neurons were shown to respond when a monkey is presented with an object, and mirror neurons responded when the monkey witnessed an object-directed action. Mirror neurons are subsequently divided into two types: strictly congruent, in which the same neuron fires during the observation of an action as well as during the execution of the same action; and, broadly congruent which are neurons that fire during observation but do not necessarily fire while executing the same motor performance (do not confuse with canonical which fire upon viewing and object and broadly congruent which fire upon viewing an action) (Gallese et al. 1996). Kohler and colleagues (2002) report that mirror neurons will fire during a given movement made by a demonstrator, even when the monkey is unable to see part of the movement. A neuron responds when a demonstrator reaches for an object; however when the demonstrator reaches for nothing, the neuron will not respond. Interestingly, when an object is hidden behind a screen, and the researcher reaches behind the screen, the neuron will respond even though the subject could not see the hidden object. Premotor mirror neurons can reason in this way, meaning that the motor representation of an action performed by others can be internally generated, even when the visual description of the action is incomplete (Umilta et al. 2001). This finding also reveals that primates have the capacity of object permanence, which demonstrates an understanding that objects continue to exist when the object is out of sight (Piaget, 1971). Such a result suggests that mirror neuron activation could be at the root of action recognition. Mirror neurons are specialized to respond only when a biological effector (such as a hand or mouth) interacts with an object, and will fail to respond at the sight of an object alone, the interaction between two non-biological objects (such as a pincher grabbing a ball), or a biological effector performing actions that are not object oriented (such as reaching toward nothing) (Rizzolatti & Craighero, 2004). The exclusive role of responding to biological effector may provide evidence that mirror neurons mediate action understanding, that is, the understanding of others behavior: Buccino (2003) points out that each time an individual sees an action done by another individual, neurons representing that specific action for themselves are activated in the observer’s premotor cortex. This automatically induced motor representation of the observed action corresponds to that which is spontaneously generated during active action and whose outcome the acting individual knows. Thus, there is a good chance that the mirror system transforms visual information into knowledge (Rizzolatti et al 2001). It may be a portentous claim that DiPellegrino makes regarding recent mirror neuron findings; alluding to evidence that premotor neurons can retrieve movements not only on the basis of stimulus characteristics, but also on the basis of the meaning of the observed actions. However, the notion that communicative actions derived from object-directed actions is not a new one. Vygotski (1934) postulates that the evolution of pointing movements was a likely derivative of attempts of children to grasp objects out of reach. Reconsidering Kohler demonstrations in the context of communicative actions, two points should be made. One is that even when the object is hidden behind a screen, the neuron will discharge; thus, the breaking of a visual relationship between the target and the effector leads to inference. If visual relationships are inconsequential (i.e. can be replaced to a certain extent by inference) in the ability to understand the meaning of an action, the precondition for understanding pointing, is a capacity already present in the primate lineage. The second is that mirror neurons discharge only when the monkey "thinks" that an action has a purpose, which creates a filter between meaningful action or communication and the milieu of background noise. Certainly evidence supports that through this mechanism, actions done by one individual can be translated into a message understood by an observer (Rizzolatti & Craighero, 2004). Gestural communication has been theorized as the evolutionary precursor to speech and language (Armstrong et al. 1995). Incidentally, the premotor F5 area in monkeys is homologous to the human Broca's area (Buccino, 2003) and extends upward to the superior frontal sulcus (Rizzolatti & Arbib, 1998). The Broca's area in humans contributes to the production of speech, so it is likely that mirror neurons in this region have been co-opted to help with the arduous task of speech/language communication. Evidence from recent studies reveals a connection between hand movement and speech articulation (see Meister et al. 2003, Gentilucci et al. 2003). This may be thought of as a linking of systems in the evolutionary transfer between mechanisms used for gestural communication and those used for language. The major difference between gesture and speech is in modality processing (i.e. visual vs. auditory). Rizzolatti and Craighero point out in a 2004 review that if mirror neurons mediate action understanding, their activity should reflect the meaning of the action that was attended to, not it's visuals features. Consequently, Kohler (2002) addressed this hypothesis by having a monkey observe a noisy action (e.g. ripping a piece of paper), and then recording neuron activation when an auditory sample of the sound was replayed. The results showed 15% of the mirror neurons that responded during the presentation of the ripping action were also active during the sound-only trials. These findings indicate the possibility that if an action is comprehensible through any sensory modality, a discharge of mirror neurons responsible for that internalized behavior is initiated. Thereupon, the nexus was found between audition and understanding; have humans somehow hijacked this system to convert abstract sound into something understood by the observer? This should be one of those exhausting questions that we should want to find an answer. So what would happen if this group of neurons were to somehow malfunction? One might predict that deficits in action understanding, verbal comprehension, and communication in general would follow. It has been hypothesized that, because mirror neurons are an integral part of the action recognition system, irregularities in this region may be the underlying cause of Autistic Spectrum Disorders, which display many of these symptoms (Williams et al. 2001). Because autism is so complex, it is likely the result of many causes (i.e. genetics, environment, infections, metabolic factors); however, it is typical for parents to cite similar behavioral anomalies. Generally they mention that their baby seems unresponsive to people or focuses intently on one (non-biological) item for long periods of time (NIMH, 2006). The National Institute of Mental Health characterizes Autism by impairments in social interaction, imaginative ability, and repetitive and restricted patterns of behavior. No matter what causes these behavioral abnormalities, it is likely that the mirror neuron system is somehow compromised. Williams (2001) cites 21 experimental studies where the ability for autistic children to imitate has been impaired. Recent brain imaging evidence published in Nature has shown that the mirror neuron system in autistic children is vastly under-active during action observation providing translational evidence that correlates their behavior with physiological data (Dapretto, 2006). Clearly, the failure to develop an intact mirror neuron system hinders an adolescent's ability to acquire important information needed to mature and produce normal human behavior.
The Spatial Neuron System According to Einstein's theory of relativity, space and time have no real distinction (Logunov, 2005); however, animals still seem to utilize this idea of space for many of their daily activities including: foraging for food, building nests, and driving to the chemist's. If there is no distinction between space and time, then what is space? Luckily, Douglas Adams from The Hitchhiker's Guide to the Galaxy is able to explain:
Space is big. You just won't believe how vastly, hugely, mind-bogglingly big it is. I mean, you may think it's a long way down the road to the chemist's, but that’s just peanuts to space.
In the 1930s neobehaviorist researchers began to investigate how animals are so effective navigating this "mind-bogglingly big" expanse called space. During this period of behaviorism and S-R dominant theorization, little attention was afforded to the internal processes of the mind (Watson & McDougall, 1929). This pattern of thought would prevail for the next decade, until Tolman (1948) proposed that an intermediary between a stimulus and a response must be capable of storing information. He also predicted that this apparatus might have the capability of forming cognitive maps of the environment. Although this theory met considerable skepticism at the time, O'keefe and Nadel (1978) revived this idea in an influential book about the possible neural correlates of spatial coding (see Lieberman, 2000). According to O'Keefe (1971), the answer to spatial coding may reside in a collection of neurons in the limbic system dubbed place cells (PCs). Found predominately in the hippocampus and surrounding structures, these neurons have been shown to increase their firing rate when an animal is located in a particular region of its environment. There are several different classes of these spatial neurons, each with a slightly different function. True PCs are pyramidal neurons in the CA1 and CA3 regions of the hippocampus that fire when an animal is in a particular spatial location or "place-field" (O'Keefe & Dostrovsky, 1971). When the subject moves throughout the environment each adjacent pyramidal neuron will increase its firing rate when moving into the associated place field and decrease its firing rate after moving out of the place field. To depict the intricate relationship between PCs and an animals external environment one must examine the relationship between the small and circumscribed place-fields as they relate to neuronal firing rates (Best & White, 1998). Once in a particular place-field a PC can fire over 20 times a second; however, when the animal leaves the region the neuron can be so quiescent as to fire less than once a minute (Best & Thompson, 1989). Several studies tested PC firing rates using the radial arm maze, in order to elucidated some of their fundamental qualities. Findings from this research suggest that these neurons are able to integrate cues across different sensory modalities (e.g. visual, auditory, tactile, proprioceptive) to triangulate its location. Further, Muller and Kubie (1978) demonstrated that if salient cues are rotated around maze it would follow with an appropriate rotation of the place-fields on the hippocampus in response to the environmental change. It is an important concept, to know where we are in the world. David Foster and Matthew Wilson (2006) wondered how organisms can remember with such accuracy, their location in the environment. According to Foster and Wilson's report, the answer may reside in the reverse replay of behavioral sequences in the hippocampus. Reverse replay is when neurons fire in the opposite order from when they were originally activated and has been proposed to be a mechanism by which information is retained. The re-potentiation of neurons can help to aid in the long-term potentiation process that is associated with learning. Temporally sequenced replay has been found in sleeping rats, but hitherto this phenomenon has not been observed during the awake state (Lee & Wilson, 2002). Indeed, it would be a very short day if we could not remember how to get home from the chemist's until we fell asleep. Hence, the basic theory behind reverse replay is that it gives the lucid organism a way to consolidate information in situ. This allows the preceding events to be evaluated immediately and in precise temporal succession following a pause in active behavior. This process utilizes an anchoring event that is followed by the current behavior, and may be considered the integral mechanism for learning about experiences that just happened a moment ago. Assuming that place cells are the neural correlates of spatial processing, it should follow that damage to this region would have an impact on a subject's ability to interpret spatial information. This is precisely what Matthews (1999) demonstrated in his study comparing spatial and non-spatial learning in rats. Following a dose dependent amount of ethanol administration, rats were trained to perform a particular task using the radial arm maze. Administration of ethanol, known to have a high affinity for inhibiting the function of hippocampal structures (Thomas et al. 2004), effectively impaired the subjects' ability to learn using spatial cues. Interestingly, when spatial information was manipulated while non-spatial cues remained constant, those animals impaired by ethanol proved better on the task compared to controls (due to their forced use of relatively unimpaired non-spatial learning). This demonstrated a significant bias to use spatial information when available and switch to non-spatial information in the absence of spatial references (Silvers et al. 2003). The findings over the last few decades provide evidence that there is an intimate relationship between the hippocampus and spatial processing capabilities. Based on many preliminary discoveries, it was hypothesized that the hippocampus is used to form a cognitive map of the environment. However, partially due to the complexity of hippocampal processing and partially due to the limitations in previous studies, current knowledge provides a less concise model of hippocampal functioning. Fenton and Muller (1998) demonstrated a renewal of the place field upon reentry to a particular environment. Further evidence has shown the importance of the hippocampus in non-space related learning tasks (Best & White, 1998). Even though the cognitive mapping theory may require several caveats or manipulations, it still provides a reliable and observable neural correlate to spatial processing.
Discussion Does a colorful, voxel light overlay on a talirached brain in an fMRI study explain that in humans, a part of the mirror neuron system plays a role in the prediction or understanding of syntactic related events, regardless if they were performed or observed? If the same neuron fires during an action as well as when witnessing an action, does this provide incite about the mechanism for which an organism uses to gain knowledge about what others are doing? A researcher hears static like noise coming from a speaker attached to a microelectrode. Is that the sound of a cognitive map trying to retain information in situ? A chemist attaches several extra neutrons to an atom in a piece of radioactive mRNA. When this mRNA releases photons, causing the over-exposure of Kodak film, can we assume that neurogenesis is the key to learning? The answer is no, yes, and the ultimate publication and grant conclusory remark: we need more research. One might assume (particularly a first year graduate student) that we understand so much about psychology; it might be nearly impossible to discover something new. Their next conjecture should involve why, with our vast expanse of knowledge, we haven’t been able to attenuate abnormalities in the behavior of patients diagnosed with disorders such as autism or visual neglect. So it continues with the model of our antiquity, we delve into the minds of those who have “lost” a piece of the proverbial human experience, in order to help us explain, correlate, and expand our knowledge of brain function and it’s role in shaping our perception of the world. Should it be incongruous that we discover something about normality along the way? No, we have but one simple goal, and that is to know everything… about everything. Ironic are the matters of neuroscientists; learning about learning, trying to understand how we understand, and using the brain to ask questions about the brain. Really, what does it all this science mean? To the ape, the rat, and the guinea pig it means, at the least -- nothing, at the most -- peanuts. However, to the insightful and clever researcher it means cures to disease, treatments for syndromes, and elucidating questions about our own mind. I have never stumbled upon a deaf ear when it comes to talking about the mind. The capacity of the human brain is inherently fascinating; which gives rise to interest in the average person and has become the obsession neuroscientists. People are curious, nosy, and sometimes even inquisitive, but what should we hope to find from all our probing? In my opinion, humans are in the business of finding truth. Not poorly defined and incomplete truths, but fully developed, translational research based truths that start with small connections and blossom into broadly encompassing theories. The attempt is not to depict the phenomenally variegated human behavior as simply the result of one or two groups of neurons. Instead, by studying the behavior of individual neurons, how they communicate, how they store information, and how they respond to stimuli, we are providing ourselves with one piece of the puzzle. Correlating the activities of individual neurons with the actions of an organism is not enough to supply the final answer about how behavior is manifested. The hope is that this research might provide vital information about why, when millions of electrically friscillating action potentials organize themselves in such a way, does it produce a mind capable of learning about itself.
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