sensory and motor diseases of the brain), neurosurgery (the study of the surgical treatment of neurological disease), and psychiatry (the study of behavioral, emotional, and mental diseases). Other fields of medicine also make important contributions to neuroscience, including neuroradiology, which is the use of radiation for imaging the brain—initially with X-rays and, more recently, with positron emitters, radiofrequency, and electromagnetic waves—for clinical studies and microscopic study of samples from diseased neural tissue.
At the molecular level, one examines the interaction of molecules—typically proteins—that regulate gene expression and translation into proteins. Proteins mediate neurotransmitter synthesis and storage and release other essential neuronal molecular functions such as the receptors by which neurons respond to neurotransmitters. Most drugs used for the treatment of neurological or psychiatric diseases work by either enhancing or diminishing the effects of neurotransmitters.
At the cellular level of neuroscience, one examines the interactions between neurons through their synaptic connections and between neurons and the supporting cells, the glia. Research at the cellular level strives to determine the neural pathways by which specific neurons are connected and which of their most proximate synaptic connections might mediate a behavior or behavioral effects of a given experimental perturbation.
At the systems level, one examines the interconnected neural pathways that integrate the body’s response to environmental challenges. The sensory systems include the specialized senses for hearing, seeing, feeling, tasting, and balancing the body. The motor systems control trunk, limb, eye, and fine finger motions. Internal regulatory systems are responsible for, among other things, control of body temperature, cardiovascular function, appetite, and salt and water balance.
At the behavioral level of neuroscience research, one examines the interactions between individuals and their collective environment. Research at this level centers on the systems that integrate physiological expressions of learned, reflexive, or spontaneous behavioral responses. Behavioral research also looks at the cognitive operations of higher mental activity, such as memory, learning, speech, abstract reasoning, and consciousness. Research over the past three decades has established that the brain is highly adaptable (this ability is commonly termed “neuroplasticity”) at each level of operation: the activity-dependent ability to change gene expression, to change transmitter production and response, to change cellular structure and strength of connections between neurons, and to change behaviors by learning.
An important consequence of organizing neuroscience research at four vertical hierarchical levels is that it enables one to hypothesize experimental results on one level based on experimental findings and observations from other levels. This ability extends to hypothesizing neuronal operations or neuronal diseases based on data that would predict results at the behavioral level given the results of a perturbation or other experimental manipulation at a lower level. Such results are strongly supported in the literature (Aston-Jones and Cohen, 2005a, 2005b).
One might predict from experimental results in animals, for example, that the thin axons that establish functional properties of the noradrenergic system might also be one of the brain fiber systems most vulnerable to the percussive damage of traumatic brain injuries (TBI), such as might result from an improvised explosive device (IED). As discussed in the Chapter 5 section on brain injury, this is indeed the case, and the ability to translate between levels of neuroscience has proven helpful in the treatment of TBI and its emotional effects.
Until the advent of modern computer-based technology, the primary noninvasive tools used to understand the workings of the central and peripheral nervous system were the recording of electrical signals from the scalp (electroencephalography [EEG]) and X-ray imaging of the soft tissue of brain as distinguished from bone and compartments containing cerebral spinal fluid (CSF). EEG allowed detecting epileptogenic foci that could subsequently be managed surgically if a discrete region was involved in the initiation of seizures or pharmacologically if the region was more generalized. The X-ray imaging allowed detection and localization of lesions because the lesions displaced readily identified portions of the brain. However, these technologies provided very limited insight into neural information processing related to cognition, the central mechanisms involved in the perception of pain, or other higher-order brain activities. The pioneering work of Penfield and his colleagues was an exception: It combined EEG with invasive brain surgery to associate the visual and auditory auras that accompanied seizures to specific regions in the visual, auditory, or temporal cortices (Penfield and Perot, 1963).
The two decades from the late 1980s to the present have seen the rapid rise of technologies that can provide high-resolution structural images of the gray and white matters of brain as distinct from one another, clearly delineating details as small as the foci of white-matter disease and inflammatory changes. These technologies are capable of imaging the metabolic processes that are associated with functional activity of the brain in response to specific stimuli (positron emission tomography [PET] and functional magnetic resonance imaging [fMRI]); the orientation and dimensions of axonal fiber bundles connecting one brain region to another (diffusion tensor imaging); and the electrophysiological localization of brain activation (magnetoencephalography