James R. Augustine

Circuitry and functional aspects of the insular lobe in primates including humans.

The progress made in understanding the insula in the decade following an earlier review (Augustine, Neurol. Res., 7 (1985) 2-10) is examined in this review. In these ten years, connections have been described between the insula and the orbital cortex, frontal operculum, lateral premotor cortex, ventral granular cortex, and medial area 6 in the frontal lobe. Insular connections between the second somatosensory area and retroinsular area of the parietal lobe have been documented. The insula was found to connect with the temporal pole and the superior temporal sulcus of the temporal lobe. It has an abundance of local intrainsular connections and projections to subdivisions of the cingulate gyrus. The insula has connections with the lateral, lateral basal, central, cortical and medial amygdaloid nuclei. It also connects with nonamygdaloid areas such as the perirhinal cortex, entorhinal, and periamygdaloid cortex. The thalamic taste area, the parvicellular part of the ventral posteromedial nucleus, projects fibers to the ipsilateral insular-opercular cortex. In the past decade, confirmation has been given to the insula as a visceral sensory area, visceral motor area, motor association area, vestibular area, and language area. Recent studies have expanded the role of the insula as a somatosensory area, emphasizing its multifaceted, sensory role. The idea of the insula as limbic integration cortex has been affirmed and its role in Alzheimers disease suggested.

Neuropeptide Y and somatostatin-like immunoreactivity in neurons of the monkey amygdala

Neurons in the monkey amygdala exhibiting neuropeptide Y-like immunoreactivity and somatostatin-like immunoreactivity were identified using an avidin-biotin immunohistochemical technique. Differential co-existence of the two peptides was demonstrated using two-color immunoperoxidase and adjacent section methods. Numerous neuropeptide Y-positive neurons were observed in the basolateral and superficial amygdaloid nuclei. A moderate number of neuropeptide Y-positive neurons was seen in the medial subdivision of the central nucleus, but only a few neurons were observed in the lateral subdivision. Numerous somatostatin-positive neurons were stained in all major amygdaloid nuclei and always outnumbered neuropeptide Y-positive cells. All amygdaloid nuclei contained numerous peptide-positive fibers whose density varied depending on the nucleus. Approximately 90% of neuropeptide Y-positive neurons also exhibited somatostatin-like immunoreactivity. The percentage of somatostatin-positive neurons that exhibited neuropeptide-Y immunoreactivity varied in different nuclei. In the superficial amygdaloid nuclei, medial subdivision of the central nucleus and most portions of the basolateral nuclei the predominant cell type stained with both the neuropeptide Y and somatostatin antibodies was a spine-sparse non-pyramidal neuron. In the dorsal portion of the lateral nucleus, however, most peptide-positive neurons had spiny dendrites. Only the cell bodies and proximal dendrites of somatostatin-positive neurons in the lateral subdivision of the central nucleus were immunostained. This study demonstrates that specific cell populations in the primate amygdala contain neuropeptide Y, somatostatin or both peptides. Most peptide-positive neurons in the basolateral and superficial amygdaloid nuclei appear to be local circuit neurons that contribute to the dense plexus of peptide-positive axons in these regions. The finding of neurons with spiny dendrites in the dorsal part of the lateral nucleus suggests that these cells may be functionally different from peptide-positive neurons in other portions of the basolateral amygdala. The lateral subdivision of the central nucleus is distinguished from other amygdaloid nuclei by containing a large population of somatostatin-positive neurons that do not exhibit neuropeptide Y immunoreactivity.

Behavioral, anatomical, and physiological aspects of recovery of motor function following stroke

Restoration of motor function is relatively common in humans and non-human primates. Studies of the behavioral aspects of recovery indicate that responses re-emerge in a fixed sequence that resembles initial acquisition. The extent to which this occurs depends on factors unique to the subject. Research suggests that the traditional view of a hierarchically organized brain is inaccurate. Instead, the brain is comprised of parallel circuits which may be disinhibited and/or recruited when damage occurs. In some cases, damage leads to reorganization of cerebral cortical maps. Available data point to the utility of interventions to promote recovery. Research suggests that recovery from other forms of impairment (e.g., non-vascular lesions or impairment in language) involves similar processes.

Evolution and Rebirth of Functional Stereotaxy in the Subthalamus

The first human stereotactic surgery based on intracerebral landmarks and Cartesian coordinates was performed in 1947. With this followed the publication of a number of stereotactic frames and atlases. The intercommissural line joining the anterior and posterior commissures was to define stereotactic coordinate systems used in movement disorders and other functional neurosurgical procedures. Initially the target for Parkinson disease was the globus pallidus internus (GPi), but many investigators soon turned to the thalamus or parts of the subthalamus, but not the subthalamic nucleus. Microelectrode recording was introduced in 1961. With the apparent clinical efficacy of L-DOPA in 1965 interest in stereotactic surgery for Parkinson disease declined. The failure of prolonged, consistent pharmacologic management of bradykinesia and tremor, the side effects of dyskinesias, and the fading therapeutic success of medical treatment of movement disorders led to a resurgence of interest in the surgical management of movement disorders. With advances in understanding of the functional anatomy of the corticobasal ganglia circuit, advances in brain imaging, more sophisticated electrophysiologic recordings, and the use of deep brain stimulation as a reversible lesion, stereotactic surgery returned as a viable option for the treatment of movement disorders. The posterior medial part of the globus pallidus, ventral intermediate nucleus of the thalamus, and the subthalamus, its nuclei and pathways, are sites for interrupting pathophysiologic circuits. Not only has this been applied to movement disorders, but to epilepsy, chronic pain, and behavioral disorders.

A lucite plate method for 3-dimensional reconstruction of neuronal populations

A Lucite plate reconstruction method is described which, when combined with HRP histochemistry, provides an excellent means of visualizing, in 3-dimensional fashion, the functional organization of neuronal populations. Color photomicrographs of representative serial sections were made through the baboon oculomotor nucleus. Each color slide was then projected onto a 9 X 12 in. Lucite plate and the configuration of the nucleus at each representative level drawn to scale on the plates. These plates were then stacked one in front of the other yielding a see-through, 3-dimensional reconstruction of the entire nucleus. Color transparencies of every sixth HRP-processed section were made and the image of each section projected onto the Lucite plates on which the configuration of the oculomotor nucleus was previously outline. Using different colored stars to represent the neurons which supply different oculomotor muscles, the number and location of HRP-positive neurons was then plotted. The end result was an anatomically accurate 3-dimensional reconstruction of the entire labeled population of the oculomotor nucleus including the location of subnuclei that can be viewed from any side or at any angle. With adequate reference points these data can be entered into a computer graphics device, then viewed and manipulated in 3-dimensional fashion.

Immunocytochemical staining of neuropeptide Y (NPY) in the insular lobe of the monkey: a light microscopic study

Neuropeptide Y (NPY) has been detected immunocytochemically in cerebral cortex and subcortical white matter of the primate frontal, parietal, temporal, and occipital lobes. Because little is known about NPY in the primate insular lobe and because peptides play an important role in normal neuronal functioning and alterations in brain peptides are associated with certain neurological diseases, we studied the presence, distribution, and structural characteristics of NPY-immunostained elements at the light microscopic level in the insula of Macaca fascicularis. We used free-floating sections, rabbit anti-porcine NPY serum, and the avidin and biotinylated peroxidase complex technique. Neuropeptide Y-immunostained neurons were demonstrated in layers II, III, and V/VI, and in the adjoining subcortical white matter. Immunostaining was localized to neuronal somata, neuronal processes, and a delicate plexus in the neuropil. The majority of NPY-immunostained neurons were non-pyramidal, had round somata 10-20 microns in major transverse diameter, and two or three neuronal processes. Computer-aided quantitative analysis of the length, breadth, and area of NPY-stained neurons was performed. Our findings are consistent with observations by others on the presence, laminar distribution, and structural characteristics of NPY-immunostained elements at the light microscopic level in other cerebral lobes of non-human primates.

Immunocytochemical staining of GABA in the insular lobe of the savanna baboon: a light microscopic study

The free floating peroxidase antiperoxidase (PAP) technique has been applied to sections of the baboon insular cortex using an antibody for gamma-aminobutyric acid (GABA). Immunostaining was localized to neuronal processes, punctate structures in the neuropil, and neuroglial cells in the subcortical white matter. GABAergic neurons were present in all cortical layers (especially layers II, III, and V/VI), in the subcortical white matter, and at all insular levels. Individual GABA-immunostained nerve cell bodies were non-pyramidal in type, often vertically oriented, round or pear-shaped, and 7.5-12.5 microns in their major transverse diameter. In the deepest cortical layers larger GABA-positive neurons were present. Horizontal GABA-positive cells were rarely identified. Immunostained neurons with apically oriented processes, basally directed processes, bipolar neurons, and multipolar neurons (10-12.5 microns in major transverse diameter) were also identified. Pyramidal shaped cells (measuring 17.5-18.5 micron) and the proximal portions of their processes were often outlined by puncta. GABA-immunostained cells in the subcortical white matter typically had a long but narrow shape. These GABAergic neurons are considered to be intrinsic or local circuit neurons.