Cortical projections to the superior colliculus in grey squirrels (Sciurus carolinensis).

The superior colliculus is an important midbrain structure involved with integrating information from varying sensory modalities and sending motor signals to produce orienting movements towards environmental stimuli. Because of this role, the superior colliculus receives a multitude of sensory inputs from a wide variety of subcortical and cortical structures. Proportionately, the superior colliculus of grey squirrels is among the largest in size of all studied mammals, suggesting the importance of this structure in the behavioural characteristics of grey squirrels. Yet, our understanding of the connections of the superior colliculus in grey squirrels is lacking, especially with respect to possible cortical influences. In this study, we placed anatomical tracer injections within the medial aspect of the superior colliculus of five grey squirrels (Sciurus carolinensis) and analysed the areal distribution of corticotectal projecting cells in flattened cortex. V1 projections to the superior colliculus were studied in two additional animals. Our results indicate that the superior colliculus receives cortical projections from visual, higher order somatosensory, and higher order auditory regions, as well as limbic, retrosplenial and anterior cingulate cortex. Few, if any, corticotectal projections originate from primary motor, primary somatosensory or parietal cortical regions. This distribution of inputs is similar to the distribution of inputs described in other rodents such as rats and mice, yet the lack of inputs from primary somatosensory and motor cortex is features of corticotectal inputs more similar to those observed in tree shrews and primates, possibly reflecting a behavioural shift from somatosensory (vibrissae) to visual navigation.

Cortical cell and neuron density estimates in one chimpanzee hemisphere.

The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.

Distributions of Cells and Neurons across the Cortical Sheet in Old World Macaques.

According to previous research, cell and neuron densities vary across neocortex in a similar manner across primate taxa. Here, we provide a more extensive examination of this effect in macaque monkeys. We separated neocortex from the underlying white matter in 4 macaque monkey hemispheres (1 Macaca nemestrina, 2 Macaca radiata, and 1 Macaca mulatta), manually flattened the neocortex, and divided it into smaller tissue pieces for analysis. The number of cells and neurons were determined for each piece across the cortical sheet using flow cytometry. Primary visual cortex had the most densely packed neurons and primary motor cortex had the least densely packed neurons. With respect to differences in brain size between cases, there was little variability in the total cell and neuron numbers within specific areas, and overall trends were similar to what has been previously described in Old World baboons and other primates. The average hemispheric total cell number per hemisphere ranged from 2.9 to 3.7 billion, while the average total neuron number ranged from 1.3 to 1.7 billion neurons. The visual cortex neuron densities were predictably higher, ranging from 18.2 to 34.7 million neurons/cm2 in macaques, in comparison to a range of 9.3-17.7 million neurons/cm2 across cortex as a whole. The results support other evidence that neuron surface densities vary across the cortical sheet in a predictable pattern within and across primate taxa.

Epileptic baboons have lower numbers of neurons in specific areas of cortex.

Epilepsy is characterized by recurrent seizure activity that can induce pathological reorganization and alter normal function in neocortical networks. In the present study, we determined the numbers of cells and neurons across the complete extent of the cortex for two epileptic baboons with naturally occurring seizures and two baboons without epilepsy. Overall, the two epileptic baboons had a 37% average reduction in the number of cortical neurons compared with the two nonepileptic baboons. The loss of neurons was variable across cortical areas, with the most pronounced loss in the primary motor cortex, especially in lateral primary motor cortex, representing the hand and face. Less-pronounced reductions of neurons were found in other parts of the frontal cortex and in somatosensory cortex, but no reduction was apparent in the primary visual cortex and little in other visual areas. The results provide clear evidence that epilepsy in the baboon is associated with considerable reduction in the numbers of cortical neurons, especially in frontal areas of the cortex related to motor functions. Whether or not the reduction of neurons is a cause or an effect of seizures needs further investigation.

Neuron densities vary across and within cortical areas in primates.

The numbers and proportion of neurons in areas and regions of cortex were determined for a single cortical hemisphere from two prosimian galagos, one New World owl monkey, one Old World macaque monkey, and one baboon. The results suggest that there is a common plan of cortical organization across the species examined here and also differences that suggest greater specializations in the Old World monkeys. In all primates examined, primary visual cortex (V1) was the most neuron-dense cortical area and the secondary visual areas had higher-than-average densities. Primary auditory and somatosensory areas tended to have high densities in the Old World macaque and baboon. Neuronal density varies less across cortical areas in prosimian galagos than in the Old World monkeys. Thus, cortical architecture varies greatly within and across primate species, but cell density is greater in cortex devoted to the early stages of sensory processing.

Effect of Dexmedetomidine on Perception of Paresthesia during Subthalamic Nucleus Deep Brain Stimulation Surgery for Parkinson's Disease.

Background: Deep brain stimulation (DBS) has become a well-established treatment for the management of Parkinson's disease (PD). The most common method of lead targeting utilizes microelectrode recording (MER) and intraoperative macrostimulation to confirm accurate placement of the lead. This has been significantly aided by the use of dexmedetomidine (DEX) sedation during the procedure. Despite the frequent use of DEX, it has been theorized that DEX may have some effects on the MER during intraoperative testing. The effect on the perception of sensory thresholds during macrostimulation in the form of paresthesia is still unreported. Objectives: To investigate the effect of the sedative DEX on sensory perception thresholds observed in the intraoperative versus postoperative settings for patients undergoing subthalamic nucleus (STN) DBS surgery for PD. Materials and Methods: Adult patients (n = 8) with a diagnosis of PD underwent placement of DBS leads (n = 14) in the STN. Patients were subjected to intraoperative macrostimulation for capsular and sensory thresholds prior to placement of each DBS lead. These were compared to sensory thresholds observed in the postoperative setting during outpatient programming at three depths on each lead (n = 42). Results: In most contacts (22/42) (P = 0.19), sensory thresholds for paresthesia perception were either perceived at a higher voltage or absent during intraoperative testing in comparison to those observed in the postoperative setting. Conclusions: DEX appears to have measurable (though not statistically significant) effect on the perception of paresthesia observed during intraoperative testing.

Development of motor maps in rats and their modulation by experience.

While a substantial literature demonstrates the effect of differential experience on development of mammalian sensory cortices and plasticity of adult motor cortex, characterization of differential experience on the functional development of motor cortex is meager. We first determined when forelimb movement representations (motor maps) could be detected in rats during postnatal development and then whether their motor map expression could be altered with rearing in an enriched environment consisting of group housing and novel toys or skilled learning by training on the single pellet reaching task. All offspring had high-resolution intracortical microstimulation (ICMS)-derived motor maps using methodologies previously optimized for the adult rat. First, cortical GABA-mediated inhibition was depressed by bicuculline infusion directly into layer V of motor cortex and ICMS-responsive points were first reliably detected on postnatal day (PND) 13. Without relying on bicuculline disinhibition of cortex, motor maps emerged on PND 35 and then increased in size until PND 60 and had progressively lower movement thresholds. Second, environmental enrichment did not affect initial detection of responsive points and motor maps in non-bicuculline-treated pups on PND 35. However, motor maps were larger on PND 45 in enriched rat pups relative to pups in the standard housing condition. Rats in both conditions had similar map sizes on PNDs 60, 75, and 90. Third, reach training in rat pups resulted in an internal reorganization of the map in the hemisphere contralateral, but not ipsilateral, to the trained forelimb. The map reorganization was expressed as proportionately more distal (digit and wrist) representations on PND 45. Our data indicate that both environmental enrichment and skilled reach training experience can differentially modify expression of motor maps during development.

Direct Comparison of Posterior Subthalamic Area Stimulation versus Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.

In this case report, we describe successful tremor capture via stimulation of the posterior subthalamic area (PSA) for a patient with tremor-predominant Parkinson's disease. In this scenario, the patient had a deep brain stimulation (DBS) lead placed in the PSA of the right hemisphere and a DBS lead placed in the subthalmic nucleus (STN) of the left hemisphere. Therefore, we were able to directly compare tremor capture in the same patient receiving stimulation in two different brain areas. We show that both placements are equally efficacious for tremor suppression, though the DBS lead placed in the PSA required slightly higher current intensity. This comparison in the same patient confirms that stimulation of the PSA can successfully suppress tremor in Parkinson's disease.

Functional brain mapping at 9.4T using a new MRI-compatible electrode chronically implanted in rats.

There is a need for acute and chronic stimulation of the brain within the MRI for studies of epilepsy, as well as deep brain stimulation for movement and behavioral disorders. This work describes the production and characteristics of carbon fiber-based electrodes for acute and chronic stimulation in the brain. Increasing MRI field strengths are making it increasingly difficult to introduce foreign objects without a susceptibility artifact. We describe the production of, and the characteristics of carbon fiber-based electrodes. These are biocompatible and can be implanted for chronic studies. We show the use of these electrodes at 9.4T for studying functional activation. Data are presented showing regional connectivity. Activation not only occurs near the electrode, but at sites distant and often contralateral to the electrode. In addition, there were sites showing strong negative activation to stimulation both with direct stimulation and during a kindling-associated seizure.

Predicting extended hospital stay after deep brain stimulation surgery in Parkinson's patients.

BACKGROUND: The goal of deep brain stimulation (DBS) is to achieve maximal benefit for the patient while minimizing the likelihood of adverse effects. Currently, no standardized criteria exist that predicts extended hospital stay in DBS patients, although careful patient selection is recognized as a very important step for successful DBS therapy. OBJECTIVES AND METHODS: The objective of this study was to identify eight key factors that predicted extended post-operative hospital stay following DBS lead implantation, in an effort to better identify patients that would require minimal hospital stay, resulting in reduced cost and reduced exposure to hospital- related problems. Univariate logistic regression models were used to examine associations between each factor and patients' post-surgical outcomes. RESULTS: Using data collected from 183 patients, we found that 53 patients required a hospital stay longer than two days within one month post-procedure. Those who were 70 years or older and those who had frequent falls were significantly more likely to require extended post-surgical care. Patients that scored three points or higher on our eight-factor assessment scale had a greater likelihood of experiencing an event that would require an extended hospital stay following DBS lead placement, regardless of what three factors were present. CONCLUSIONS: Any PD patient who is 70 years or older, incurring frequent falls, or with more than three points on our scale, should be carefully screened and cautioned about likely prolonged recovery and extended post-operative hospital stay.