Global Neurotoxicity: Quantitative Analysis of Rat Brain Toxicity Following Exposure to Trimethyltin.

The organotin, trimethyltin (TMT), is a highly toxic compound. In this study, silver-stained rat brain sections were qualitatively and quantitatively evaluated for degeneration after systemic treatment with TMT. Degenerated neurons were counted using image analysis methods available in the HALO image analysis software. Specific brain areas including the cortex, inferior and superior colliculus, and thalamus were quantitatively analyzed. Our results indicate extensive and widespread damage to the rat brain after systemic administration of TMT. Qualitative results suggest severe TMT-induced toxicity 3 and 7 days after the administration of TMT. Trimethyltin toxicity was greatest in the hippocampus, olfactory area, cerebellum, pons, mammillary nucleus, inferior and superior colliculus, hypoglossal nucleus, thalamus, and cerebellar Purkinje cells. Quantification showed that the optic layer of the superior colliculus exhibited significantly more degeneration compared to layers above and below. The inferior colliculus showed greater degeneration in the dorsal area relative to the central area. Similarly, in cortical layers, there was greater neurodegeneration in deeper layers compared to superficial layers. Quantification of damage in various thalamic nuclei showed that the greatest degeneration occurred in midline and intralaminar nuclei. These results suggest selective neuronal network vulnerability to TMT-related toxicity in the rat brain.

Quantitative neurotoxicology: Potential role of artificial intelligence/deep learning approach.

Neurotoxicity studies are important in the preclinical stages of drug development process, because exposure to certain compounds that may enter the brain across a permeable blood brain barrier damages neurons and other supporting cells such as astrocytes. This could, in turn, lead to various neurological disorders such as Parkinson's or Huntington's disease as well as various dementias. Toxicity assessment is often done by pathologists after these exposures by qualitatively or semiquantitatively grading the severity of neurotoxicity in histopathology slides. Quantification of the extent of neurotoxicity supports qualitative histopathological analysis and provides a better understanding of the global extent of brain damage. Stereological techniques such as the utilization of an optical fractionator provide an unbiased quantification of the neuronal damage; however, the process is time-consuming. Advent of whole slide imaging (WSI) introduced digital image analysis which made quantification of neurotoxicity automated, faster and with reduced bias, making statistical comparisons possible. Although automated to a certain level, simple digital image analysis requires manual efforts of experts which is time-consuming and limits analysis of large datasets. Digital image analysis coupled with a deep learning artificial intelligence model provides a good alternative solution to time-consuming stereological and simple digital analysis. Deep learning models could be trained to identify damaged or dead neurons in an automated fashion. This review has focused on and discusses studies demonstrating the role of deep learning in segmentation of brain regions, toxicity detection and quantification of degenerated neurons as well as the estimation of area/volume of degeneration.

Quantitative Neurotoxicology: An Assessment of the Neurotoxic Profile of Kainic Acid in Sprague Dawley Rats.

This study consisted of a qualitative and quantitative assessment of neuropathological changes in kainic acid (KA)-treated adult male rats. Rats were administered a single 10 mg/kg intraperitoneal injection of KA or the same volume of saline and sacrificed 24 or 48 hours posttreatment. Brains were collected, sectioned coronally (∼ 81 slices), and stained with amino cupric silver to reveal degenerative changes. For qualitative assessment of neural degeneration, sectioned material was evaluated by a board-certified pathologist, and the level of degeneration was graded based upon a 4-point scale. For measurement of quantitative neural degeneration in response to KA treatment, the HALO digital image analysis software tool was used. Quantitative measurements of specific regions within the brain were obtained from silver-stained tissue sections with quantitation based on stain color and optical density. This quantitative evaluation method identified degeneration primarily in the cerebral cortex, septal nuclei, amygdala, olfactory bulb, hippocampus, thalamus, and hypothalamus. The KA-produced neuronal degeneration in the cortex was primarily in the piriform, insular, rhinal, and cingulate areas. In the hippocampus, the dentate gyrus was found to be the most affected area. Our findings indicate global neurotoxicity due to KA treatment. Certain brain structures exhibited more degeneration than others, reflecting differential sensitivity or vulnerability of neurons to KA.

Saccadic Eye Movements in Young-Onset Parkinson's Disease - A BOLD fMRI Study.

The objective of the present study was to understand control of saccadic eye movements in patients with young onset Parkinson's disease (YOPD) where onset of disease symptoms appears early in life (<40 years of age). Functional magnetic resonance imaging (fMRI) was performed in patients with YOPD and control subjects while they performed saccadic tasks, which consisted of a reflexive task and another task that required inhibitory control of eye movements (Go-NoGo task). Functional imaging related to saccadic eye movements in this group of patients has not been widely reported. A 1.5T MR scanner was used for structural and functional imaging. Analysis of blood-oxygen-level-dependent (BOLD) fMRI was performed using Statistical Parametric Mapping (SPM) software and compared in patients and controls. In patients with YOPD greater activation was seen significantly in the middle frontal gyrus, medial frontal gyrus, angular gyrus, cingulate gyrus, precuneus and cerebellum, when compared with the control group, during the saccadic tasks. Gap and overlap protocols revealed differential activation patterns. The abnormal activation during reflexive saccades was observed in the overlap condition, while during Go-NoGo saccades in the gap condition. The results suggest that impaired circuitry in patients with YOPD results in recruitment of more cortical areas. This increased frontal and parietal cortical activity possibly reflects compensatory mechanisms for impaired cognitive and saccadic circuitry.

Impact of patient-centred home telehealth programme on outcomes in heart failure.

BACKGROUND: Telehealth is a promising intervention to reduce readmissions and healthcare-associated costs in patients with heart failure. METHODS: We performed a retrospective analysis of the impact of telehealth on 197 heart failure patients who had successfully completed one year of home telehealth monitoring following a heart failure admission as part of a clinically mandated programme at a Veterans Affairs Medical Center. Outcomes were compared both within the group (one year before and one year after home telehealth monitoring), and to a contemporary control cohort of 870 heart failure patients who were admitted but not enrolled in home telehealth. The following outcomes were analysed: admissions for any cause, heart failure admissions, total hospital days per patient, average length of stay per admission, urgent care and emergency room visits, and primary care visits. RESULTS: Both the home telehealth and control cohorts consisted of older male patients. Total hospital days per patient was significantly reduced by home telehealth monitoring in the home telehealth group (2.4 ± 3.5) in comparison to the previous year without monitoring (4.1 ± 4.6, p < 0.0001) and to the control group (3.8 ± 5.3, p < 0.001). A significantly lower admission rate (1.1 ± 1.6) and length of stay (5.7 ± 11.3 days) were observed during home telehealth monitoring within the home telehealth group compared to the prior year (1.6 ± 1.7, p < 0.05 and 9.5 ± 14 days, p < 0.01 respectively) but not in comparison with the control group (1.4 ± 2.0, p < 0.07). The home telehealth group also had a significantly lower length of stay when compared to the control group (5.7 ± 11.3 vs 9.0 ± 14.9, p < 0.01). The number of urgent care and emergency room visits, or primary care visits, was not significantly different during home telehealth monitoring as compared to the prior year. CONCLUSIONS: Personalised and patient-centred home telehealth monitoring in heart failure patients was successful in reducing outcomes without an increase in outpatient and urgent care visits.

The Relationship between Saccades and Locomotion.

Human locomotion involves a complex interplay among multiple brain regions and depends on constant feedback from the visual system. We summarize here the current understanding of the relationship among fixations, saccades, and gait as observed in studies sampling eye movements during locomotion, through a review of the literature and a synthesis of the relevant knowledge on the topic. A significant overlap in locomotor and saccadic neural circuitry exists that may support this relationship. Several animal studies have identified potential integration nodes between these overlapping circuitries. Behavioral studies that explored the relationship of saccadic and gait-related impairments in normal conditions and in various disease states are also discussed. Eye movements and locomotion share many underlying neural circuits, and further studies can leverage this interplay for diagnostic and therapeutic purposes.

Saccadic eye movements in Parkinson's disease.

This review focuses on saccadic eye movement research in Parkinson's disease (PD) patients. Results from various studies related to Parkinson disease and saccades have been discussed in terms of various saccadic parameters like latency, amplitude, velocity and gain. Neural circuitry of saccadic eye movements and cognitive processes and it's relation with altered saccadic performance in Parkinson disease has been discussed here. This article also covers various research paradigms commonly used to study saccades. Effects of medication on saccadic parameters in PD patients have also been discussed along with the effects of deep brain stimulation of subthalamic nucleus on saccadic performance in PD patients. Literature review was done using online Pubmed search engine and National Medical Library.

Mechanism of selective attention: fMRI study of face-word Stroop task performance.

Selective attention is the cognitive process of selecting and processing the task relevant information and ignoring the task irrelevant information. Though the neural substrates involved in this cognitive process are well established, the mechanism of selection process is the point of contention. To study the effect of selection process on the information processing we performed functional neuroimaging on 23 healthy righthanded male subjects while performing a modified face word stroop task. The word processing area did not show any attention dependent changes in the level of activity whereas the activity of face processing area was higher when the faces were target, but there was no decrease in baseline activity when faces were distractors. Our results suggest that during selective attention there is no biasing of sensory processing for automatically processed stimuli like words whereas there is amplification of task relevant information when stimuli are processed in controlled manner.