The Neuroscientist

The spontaneous recovery of sensory, motor, and cognitive functions after stroke is thought to be mediated primarily through the reorganization and rewiring of surviving brain circuits. Given that dendritic spine turnover underlies rewiring during normal development and plasticity, this process is likely to play a key role in mediating functional changes that occur during and after stroke. Recently, a new approach has been taken using two-photon microscopy to monitor, in real time, the temporal and spatial progression of dendritic plasticity in the living animal, both while it is experiencing the initial ischemic episode as well as during long-term recovery from stroke damage. Here, we highlight recent evidence showing that stroke can trigger extensive changes in the relatively hardwired adult brain. For example, when dendrites are challenged by acute ischemia, they can disintegrate within minutes of ischemia and rapidly reassemble during reperfusion. Over longer time scales, dendrites in the surviving peri-infarct zone show heightened levels of spine turnover for many weeks after stroke, thereby raising the possibility that future stroke therapies may be able to facilitate or optimize dendritic rewiring to improve functional recovery. NEUROSCIENTIST 14(2):139—146, 2008. DOI: 10.1177/1073858407309854

During the past decade, a large body of evidence has implicated BDNF in synaptic plasticity. In this review, we focus on the newer experiments that involve BDNF in different aspects of learning and memory processing—in particular, in memory persistence and storage. NEUROSCIENTIST 14(2):147—156, 2008. DOI: 10.1177/1073858407305850

People have always been fascinated by the exquisite precision and flexibility of the human hand. When hand meets object, we confront the overlapping worlds of sensorimotor and cognitive functions. The complex apparatus of the human hand is used to reach for objects, grasp and lift them, manipulate them, and use them to act on other objects. This review examines what is known about the control of the hand by the cerebral cortex. It compares and summarizes results from behavioral neuroscience, electrophysiology, and neuroimaging to provide a detailed description of the neural circuits that facilitate the formation of grip patterns in human and nonhuman primates. NEUROSCIENTIST 14(2):157—170, 2008. DOI: 10.1177/1073858407312080

Many neuroscientists assume that ambient extracellular glutamate concentrations in the nervous system are biologically negligible under nonpathological conditions. This assumption is false. Hundreds of studies over several decades suggest that ambient extracellular glutamate levels in the intact mammalian brain are ~0.5 to ~5 µM. This has important implications. Glutamate receptors are desensitized by glutamate concentrations significantly lower than needed for receptor activation; 0.5 to 5 µM of glutamate is high enough to cause constitutive desensitization of most glutamate receptors. Therefore, most glutamate receptors in vivo may be constitutively desensitized, and ambient extracellular glutamate and receptor desensitization may be potent but generally unrecognized regulators of synaptic transmission. Unfortunately, the mechanisms regulating ambient extracellular glutamate and glutamate receptor desensitization remain poorly understood and understudied. NEUROSCIENTIST 14(2):171—181, 2008. DOI: 10.1177/1073858407308518

The area postrema is a medullary structure lying at the base of the fourth ventricle. The area postrema's privileged location outside of the blood-brain barrier make this sensory circumventricular organ a vital player in the control of autonomic functions by the central nervous system. By virtue of its lack of tight junctions between endothelial cells in this densely vascularized structure and the presence of fenestrated capillaries, peptide and other physiological signals borne in the blood have direct access to neurons that project to brain areas with important roles in the autonomic control of many physiological systems, including the cardiovascular system and systems controlling feeding and metabolism. However, the area postrema is not simply a conduit through which signals flow into the brain, but it is now being recognized as the initial site of integration for these signals as they enter the circuitry of the central nervous system. NEUROSCIENTIST 14(2):182—194, 2008. DOI: 10.1177/1073858407311100

Limb amputation results in plasticity of connections between the brain and muscles; the cortical motor representation of the missing limb seemingly disappears. The disappearance of the hand's motor representation is, however, difficult to reconcile with evidence that a perceptual representation of the missing limb persists in the form of a phantom limb endowed with sensory and motor qualities. Here, we argue that despite considerable reorganization within the motor cortex of upper-limb amputees, the representation of the amputated hand does not disappear. We hypothesize that two levels of hand-movement representation coexist within the primary motor cortex; at one level, limb movements are specified in terms of arm and hand motor commands, and at another level, limb movements are specified as muscles synergies. We propose that primary motor cortex reorganization after amputation concerns primarily the upper limb's muscular map but not its motor command map and that the integrity of the motor command map underlies the existence of the phantom limb. NEUROSCIEN-TIST 14(2):195—202, 2008. DOI: 10.1177/1073858407309466

Awareness of illness is a form of self-knowledge concerning information about the pathological state, its functional consequence, and the way it affects the patient and his interaction with the environment. Unawareness of illness has raised much interest for its consequences on compliance with treatment, prognosis, and the patient's quality of life. This review highlights the great complexity of this phenomenon both at phenomenological and etiopathogenic levels in stroke, traumatic brain injury, psychosis, dementias, and mood disorders. In particular, the clinical expression is characterized by failure to acknowledge being ill, misattribution of symptoms, and noncompliance with treatment. Unawareness of illness may also be linked with characteristics that are peculiar to each individual disturbance, such as symptom duration and cognitive impairment. Despite a long-lasting interest in the clinical characteristics of unawareness, only recently has the focus of research investigated pathogenic mechanisms, with sometimes controversial results. The vast majority of studies have pointed out a remarkable involvement of the right hemisphere. Specifically, functional and structural changes of the dorso-lateral prefrontal cortex and some other frontal areas have often been found to be associated with awareness deficit, as well as parieto-temporal areas and the thalamus, although to a lesser extent. These data indicate the present difficulty of localizing a specific cerebral area involved in unawareness and suggest the existence of possible brain circuits responsible for awareness. In conclusion, phenomenological manifestations of poor awareness are well outlined in their complexity, whereas neuroanatomic and neuropsychological findings are still too vague and sparse and need further, greater efforts to be clarified. NEUROSCIENTIST 14(2): 203—222, 2008. DOI: 10.1177/1073858407309995