GENDER DIFFERENCES IN THYROIDECTOMY-INDUCED WEIGHT LOSS AND IMPAIRED GLUCOSE LEVELS: ROLE OF L-THYROXINE.

Thyroxine, a key regulator of metabolic pathways, plays a pivotal role in glucose metabolism and the maintenance of glucose homeostasis. In clinical practice, L-thyroxine replacement therapy is commonly prescribed for patients with hypothyroidism. However, the specific effects of L-thyroxine and thyroidectomy (TX) on glucose levels remain an area of interest and investigation. In this study, 20 rats were divided into two groups (n=10 per group). The TX group (male and female rats) underwent thyroidectomy for 4 weeks. After 4 weeks, male and female thyroidectomized rats received L-thyroxine (10 µg/100 g/day, intraperitoneally) for 4 weeks. The rats' weights were monitored weekly post-surgery. Compared to the initial level, thyroidectomy resulted in weight loss, whereas L-thyroxine replacement therapy normalized the weight loss induced by thyroidectomy. Additionally, thyroidectomy led to impaired glucose levels, which were restored to normal levels with L-thyroxine treatment. These findings underscore the impact of thyroid function on glucose metabolism and highlight the potential therapeutic role of L-thyroxine.

EFFECTS OF DIMETHYL SULFOXIDE ON HIPPOCAMPAL ACTIVITY IN A ROTENONE-INDUCED RAT MODEL OF PARKINSON'S DISEASE.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease worldwide. The goal of this study was to examine the effects of dimethyl sulfoxide (DMSO) in a rat model of Parkinson's disease caused by rotenone. Due to its capacity to increase the penetration of potential water-insoluble drugs into the central nervous system, DMSO has been widely used in preclinical and clinical studies. Background and evoked spike activities were recorded in the hippocampus of rats administered DMSO (1 ml/kg i.p. for 3 weeks). We showed that pyramidal cells and Nissl bodies in the hippocampal CA1 and CA3 areas of rats administered rotenone dramatically improved after DMSO treatment. Rotenone enhanced TP and induced a milder TD effect, while DMSO also enhanced TP but induced a stronger TD effect. The analysis revealed inhibitory effects in the hippocampus in response to high-frequency stimulation (HFS; 100 Hz for 1 s) of the ipsilateral entorhinal cortex.

PRODUCTIVITY AND SELENIUM ENRICHMENT OF STEVIA IN HYDROPONIC AND SOIL CULTIVATION SYSTEMS IN THE ARARAT VALLEY.

Hydroponics offers a viable solution for obtaining plant products that are rich in micronutrients and ultramicronutrients, such as selenium. Selenium plays a crucial role in strengthening the body's immune defense and acts as a potent antioxidant. Low levels of selenium have been associated with an increased risk of heart attacks, strokes, and cancer. Stevia rebaudiana Bertoni (SrB), a relatively new crop in plant cultivation, was the focus of the present study. SrB has numerous medicinal and prophylactic properties, and its leaves are rich in macro- and microelements, vitamins, and diterpene glycosides. These diterpene glycosides, when extracted from the plant material, exhibit a sweetness that is 200-300 times greater than that of sugar. The study aimed to investigate the effects of exogenous application of varying amounts of selenium to the nutrient solution and foliar feeding of SrB plants with a selenium aqueous solution. The productivity of SrB and selenium accumulation in the leaves were assessed under both hydroponic and soil cultivation conditions in the Ararat Valley. Comparative analyses were also conducted on biometric and biochemical indicators, as well as the productivity of SrB cultivated using different fillers, including black volcanic slag, red volcanic slag, and gravel, in hydroponic and soil environments. The findings of this research hold practical significance as they serve as a foundation for the development of biotechnological approaches to enhance selenium enrichment in various crops. By applying these strategies, crop cultivation methods can be improved, and the selenium content in plant products can be enhanced. This optimization of crop production techniques can increase the nutritional value and potential health benefits of selenium-enriched plant products.

Membrane-stabilizing and protective effects of curcumin in a rotenone-induced rat model of Parkinson disease.

Parkinson disease (PD) is a chronic progressive neurodegenerative disease characterized by both motor and non-motor features. Numerous risk factors (oxidative stress, free radical formation, and several environmental toxins) have been associated with PD. The experimental studies were carried out under in vivo conditions. Biochemical data analysis indicated that compared with the parameters of control (C) rats, rotenone-induced PD rats showed a significant decrease in the specific content of the total fraction of isoforms of O2--producing, heat-stable, NADPH-containing associates (NLP-Nox) from membrane formations of tissues (brain, liver, lung, and small intestine). Compared with the C group indices, in the PD and PD + curcumin (PD + CU) groups there is some change in the shape of the optical absorption spectra of isoforms associated with a change in the amount of Nox in the isoform composition of the total fraction of the NLP-Nox associate. Thus, daily administration of CU (200 mg/kg, i.p.) to PD rats for 63 days had a regulatory effect, bringing the specific content and O2--producing activity of the total fraction of NLP-Nox isoforms closer to the norm. CU has membrane-stabilizing effects in rotenone-induced PD.

The effects of vibration on the neuronal activity of lateral vestibular nuclei in unilaterally labyrinthectomized rats.

Unilateral labyrinthectomy causes distinct oculomotor and postural disorder syndromes that gradually deteriorate. Simultaneously, compensatory mechanisms for the suppression of pathological disorders were activated. The current study aimed to investigate the characteristics of impulse activity in the ipsilateral and contralateral neurons of the lateral vestibular nucleus of unilaterally labyrinthectomized rats during various periods of vibration exposure. A program analysis of the background impulse activity of the neurons in the right- and left-lateral vestibular nuclei of rats under normal condition and after right-sided labyrinthectomy was performed. The animals were subjected to different periods of vibration exposure 2 days after surgery (5-, 10-, and 15-day periods). A comparison of the characteristics of the background impulse activity of neurons in both nuclei of intact rats revealed an initial asymmetry in the values of the mean impulse frequency and coefficient of variation of interimpulse intervals. After 5 days of vibration exposure, the values of the mean impulse frequency of neurons in both Deiters' nuclei were almost equal in labyrinthectomized rats. The mean impulse frequency of neurons on the uninjured side was higher than that on the injured side on the days following vibration exposure. The characteristics and functional significance of the findings are discussed.

Pathology and prevention of brain microvascular and neuronal dysfunction induced by a high-fructose diet in rats.

A high-fructose diet causes metabolic abnormalities in rats, and the cluster of complications points to microvascular and neuronal disorders of the brain. The aim of this study was to evaluate i) the involvement of microvascular disorders and neuronal plasticity in the deleterious effects of a high-fructose diet on the rat brain and ii) a comparative assessment of the effectiveness of Phytocollection therapy (with antidiabetic, antioxidant, and acetylcholinesterase inhibitory activities) compared to Galantamine as first-line therapy for dementia and Diabeton as first-line therapy for hyperglycemia. The calcium adenosine triphosphate non-injection histoangiological method was used to assess capillary network diameter and density. A high-fructose diet resulted in a significant decrease in the diameter and density of the capillary bed, and pharmacological manipulations had a modulatory effect on microcirculatory adaptive mechanisms. In vivo single-unit extracellular recording was used to investigate short-term plasticity in the medial prefrontal cortex. Differences in the parameters of spike background activity and expression of excitatory and inhibitory responses of cortical neurons have been discovered, allowing for flexibility and neuronal function stabilization in pathology and pharmacological prevention. Integration of the coupling mechanism between microvascular function and neuronal spike activity could delay the progressive decline in cognitive function in rats fed a high fructose diet.

Superoxide-producing thermostable associate from the small intestines of control and alloxan-induced diabetic rats: quantitative and qualitative changes.

BACKGROUND: NADPH oxidase 1 (Nox1), which is highly expressed in the colon, is thought to play a potential role in host defense as a physical and innate immune barrier against commensal or pathogenic microbes in the gastrointestinal epithelium. Diabetes can be caused by several biological factors, including insulin resistance is one of them. Alloxan is widely used to induce insulin-dependent diabetes in experimental animals. Alloxan increases the generation of reactive oxygen species as a result of metabolic reactions in the body, along with a massive increase in cytosolic calcium concentration. METHODS: Using a universal method, a superoxide radical (О2-)-thermostable associate between NADPH-containing lipoprotein (NLP) and NADPH oxidase (Nox)- NLP-Nox was isolated and purified from the small intestine (SI) of control (C) and alloxan-induced diabetic (AD) albino rats. RESULTS: In comparison to the C indices, in AD in the SI, an increase in the specific content of NLP-Nox associate and a decrease in the stationary concentration of produced О2- in liquid phase (in solution) and gas phase (during blowing by oxygen of the NLP-Nox solution) were observed. The NLP-Nox of SI associate in C and AD rats produced О2- by an immediate mechanism, using NLP as a substrate. The phenomenon of the hiding of the optical absorption maxima of the Nox in oxidized states at pH10,5 was observed in the composition of these SI associates of the C and AD rat groups. The characteristic absorption maxima of the «hidden¼ Nox were observed under these conditions after reduction by potassium dithionite. CONCLUSION: Thus, at AD, the decrease in the stationary concentration of produced О2- in the solution and gas phase was compensated for by an increase in the specific amount of associate. In addition,  the decrease in the stationary concentration of produced О2- by NLP-Nox associates at AD can be linked to a decrease in the level of NADPH in NLP-Nox composition. This could be used as a new mechanism of AD pathogenesis.

Protective effect of curcumin against rotenone-induced substantia nigra pars compacta neuronal dysfunction.

Rotenone is involved in the degeneration of dopaminergic neurons, and curcumin may prevent or effectively slow the progression of Parkinson's disease (PD). Previous research has shown that the naturally occurring phenolic compound curcumin can reduce inflammation and oxidation, making it a potential therapeutic agent for neurodegenerative diseases. The present study involves investigation of rotenone-induced histological changes in the brain area, hippocampus using Nissl staining after 35 day of subcutaneous injection of rotenone in adult male rats. We sought to determine whether curcumin could protect against rotenone-induced dopaminergic neurotoxicity in a rat model by in vivo electrical recording from Substantia nigra pars compacta (SNc). Curcumin treatment significantly improved electrical activity of neurons in the SNc of rotenone-induced PD model rats. The pattern of histological alterations corresponds with electrophysiological manifestations.

EFFECT OF SELENIUM ON EFFICIENCY AND PHYSIOLOGICAL ACTIVITY OF RADISH IN HYDROPONICS AND SOIL CULTURE IN ARARAT VALLEY1BABAKHANYAN.

The presence of the ultramicroelement Se in food is irreplaceable. Se is a component of more than 30 biologically active compounds found in humans and animals. Se levels less than 1 mg/kg have been found to be beneficial to plants. Radish is one of the most commonly cultivated vegetables worldwide and is rich in bioactive substances, vitamins, enzymes, and minerals. Radish increases resistance and protects the human body from a number of diseases, particularly diabetes, cardiovascular, and gastrointestinal diseases. The physiological multifunctional (anti-diabetic, antioxidant, and anti-inflammatory) activity of the Se-enriched plant material was also studied. This is of practical significance because the data obtained can be the basis for the development of biotechnology for the enrichment of vegetable plants with Se.

Superoxide-producing lipoprotein fraction from Stevia leaves: definition of specific activity.

BACKGROUND: Stevia rebaudiana Bertoni has various pharmacological actions, which includes antidiabetic, antioxidant, anti-inflammatory activities. The superoxide and consequently NADPH oxidase (Nox) are relevant targets involved in biological effects of Stevia. The presence of NADPH-containing superoxide-producing lipoprotein (suprol) in Stevia leaves has not yet been tested. The mechanism of producing superoxide radicals (O2-) by suprol was determined in vitro, which is associated with the electron transfer from NADPH in the composition of suprol by traces of transition metal ions (Fe3+ or Cu2+) to molecular oxygen, turning it into O2-. It is expected that the therapeutic efficacy of Stevia leaves is caused by specific activity of superoxide-producing lipoprotein fraction. METHODS: For the first time, from the dry leaves of Stevia the NADPH-containing superoxide-producing lipoprotein was isolated and purified. The specific content of suprol (milligrams in 1 g of Stevia leaves- mg/g) was determined after desalination of suprol and lyophilization. RESULTS: According to the method provided, the specific content of the isolated suprol from Stevia's leaves was up to 4.5 ± 0.2 mg / g (yields up to 68.5 ± 4.7%, p < 0.05, n = 6). Nox forms a stable complex with suprol. The optical absorption spectrum of the Nox-suprol complex represents the overlapping suprol and Nox spectra, with a certain background increase and characteristic features of optical absorption for Nox. Due to O2- producing capacity suprol-Nox complex discolors KMnO4 solutions, Coomassie brilliant blue, restores nitrotetrazolium blue to formazan and oxidizes epinephrine to adrenochrome. The oxidation activity of adrenaline is 50.3 ± 5.1 U / mg / ml (p < 0.05, n = 6). CONCLUSION: Superoxide-producing lipoprotein fraction-Nox complex from Stevia leaves (membranes) can modulate redox regulated signaling pathways and may play a positive role in type-2 diabetes by means of adrenaline oxidation mechanism.

Effects of stevia on synaptic plasticity and NADPH oxidase level of CNS in conditions of metabolic disorders caused by fructose.

BACKGROUND: Excess dietary fructose intake associated with metabolic syndrome and insulin resistance and increased risk of developing type 2 diabetes. Previous animal studies have reported that diabetic animals have significantly impaired behavioural and cognitive functions, pathological synaptic function and impaired expression of glutamate receptors. Correction of the antioxidant status of laboratory rodents largely prevents the development of fructose-induced plurimetabolic changes in the nervous system. We suggest a novel concept of efficiency of Stevia leaves for treatment of central diabetic neuropathy. METHODS: By in vivo extracellular studies induced spike activity of hippocampal neurons during high frequency stimulation of entorhinal cortex, as well as neurons of basolateral amygdala to high-frequency stimulation of the hippocampus effects of Stevia rebaudiana Bertoni plant evaluated in synaptic activity in the brain of fructose-enriched diet rats. In the conditions of metabolic disorders caused by fructose, antioxidant activity of Stevia rebaudiana was assessed by measuring the NOX activity of the hippocampus, amygdala and spinal cord. RESULTS: In this study, the characteristic features of the metabolic effects of dietary fructose on synaptic plasticity in hippocampal neurons and basolateral amygdala and the state of the NADPH oxidase (NOX) oxidative system of these brain formations are revealed, as well as the prospects for development of multitarget and polyfunctional phytopreparations (with adaptogenic, antioxidant, antidiabetic, nootropic activity) from native raw material of Stevia rebaudiana. Stevia modulates degree of expressiveness of potentiation/depression (approaches but fails to achieve the norm) by shifting the percentage balance in favor of depressor type of responses during high-frequency stimulation, indicating its adaptogenic role in plasticity of neural networks. Under the action of fructose an increase (3-5 times) in specific quantity of total fraction of NOX isoforms isolated from the central nervous system tissue (amygdala, hippocampus, spinal cord) was revealed. Stevia exhibits an antistress, membrane-stabilizing role reducing the level of total fractions of NOX isoforms from central nervous system tissues and regulates NADPH-dependent O2- -producing activity. CONCLUSION: Generally, in condition of metabolic disorders caused by intensive consumption of dietary fructose Stevia leaves contributes to the control of neuronal synaptic plasticity possibly influencing the conjugated NOX-specific targets.

Protective effects of curcumin against rotenone-induced rat model of Parkinson's disease: in vivo electrophysiological and behavioral study.

Curcumin is a naturally occurring phenolic yellow chemical isolated from the rhizomes of the plant Curcuma longa (turmeric), and is a major component of the spice turmeric. Curcumin has protective effects against rotenone-induced neural damage in Parkinson's disease (PD). The present study aims at providing new evidence for the validity of the rotenone rat model of PD by examining whether neuronal activity in the hippocampus is altered. Male albino rats were treated with rotenone injections (2.5 mg/ml intraperitoneally) for 21 days. We examined the effects of curcumin (200 mg/kg) on behavior and electrophysiology in a rat model of PD induced by rotenone. Motor activity was assessed by cylinder test. The electrical activity of neurons was measured in hippocampus. Rotenone causes significant reduction of neuronal activity. The results show that curcumin can improve the motor impairments and electrophysiological parameters and may be beneficial in the treatment of PD.

Rotenone impairs hippocampal neuronal activity in a rat model of Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative disease of unknown etiology and characterized by motor symptoms of tremor, rigidity, bradykinesia, and postural instability. Interactions between the dopaminergic systems and the hippocampus in synaptic plasticity and behavior are found. The rotenone-induced animal model is commonly used in research studies involved in PD. Administration of rotenone causes alterations of electrical neuronal activity. Rotenone (2.5 mg/kg/day) was administered intraperitoneally for 21 days to adult rats, and rotenone effects on rearing activity and electrophysiology were examined. Dose-dependent reduction of evoked neural activity and a reduction in firing strength were found in the hippocampus. Behaviorally, Rotenone rats showed a more consistent decrease in rearing across the 3 weeks, compared with animals in the control group. Thus, rotenone causes changes in hippocampal electrical activity and behavioral changes.

Protective effects of hydroponic Teucrium polium on hippocampal neurodegeneration in ovariectomized rats.

BACKGROUND: The hippocampus is a target of ovarian hormones, and is necessary for memory. Ovarian hormone loss is associated with a progressive reduction in synaptic strength and dendritic spine. Teucrium polium has beneficial effects on learning and memory. However, it remains unknown whether Teucrium polium ameliorates hippocampal cells spike activity and morphological impairments induced by estrogen deficiency. METHODS: In the present study, we investigated the effects of hydroponic Teucrium polium on hippocampal neuronal activity and morpho-histochemistry of bilateral ovariectomized (OVX) rats. Tetanic potentiation or depression with posttetanic potentiation and depression was recorded extracellularly in response to ipsilateral entorhinal cortex high frequency stimulation. In morpho-histochemical study revealing of the activity of Ca2+-dependent acid phosphatase was observed. In all groups (sham-operated, sham + Teucrium polium, OVX, OVX + Teucrium polium), most recorded hippocampal neurons at HFS of entorhinal cortex showed TD-PTP responses. RESULTS: After 8 weeks in OVX group an anomalous evoked spike activity was detected (a high percentage of typical areactive units). In OVX + Teucrium polium group a synaptic activity was revealed, indicating prevention OVX-induced degenerative alterations: balance of types of responses was close to norm and areactive units were not recorded. All recorded neurons in sham + Teucrium polium group were characterized by the highest mean frequency background and poststimulus activity. In OVX+ Teucrium polium group the hippocampal cells had recovered their size and shape in CA1 and CA3 field compared with OVX group where hippocampal cells were characterized by a sharp drop in phosphatase activity and there was a complete lack of processes reaction. CONCLUSION: Thus, Teucrium polium reduced OVX-induce neurodegenerative alterations in entorhinal cortex-hippocamp circuitry and facilitated neuronal survival by modulating activity of neurotransmitters and network plasticity.

Goji fruit (Lycium barbarum) protects sciatic nerve function against crush injury in a model of diabetic stress.

Excess fructose consumption causes changes in functioning of the central and peripheral nervous systems, which increase the vulnerability of peripheral nerves to traumatic injury. The aim of this study was to evaluate the electrophysiological parameters of responses of motoneurons of the spinal cord at high-frequency stimulation of the distal part of the injured sciatic nerve in a model of diabetic stress under action of Lycium barbarum (LB). Male albino rats were given with drinking water with 50% concentration of dietary fructose for 6 weeks. Starting on the 7th week a crush injury of the left sciatic nerve was carried out. Some of the animals received fructose post-injury for 3 weeks and some of the animals received fructose+dry LB fruits for 3 weeks. In the fructose+crush+LВ group a relatively proportional division of tetanic and posttetanic potentiation and depression in responses of ipsilateral and contralateral motoneurons was observed, which would suggest the modulatory role of LB in short-term synaptic plasticity formation. Generally, LB fruit is able to modulate central nervous system reorganization, amplifying positive adaptive changes that improve functional recovery and promote selective target reinnervation in high fructose-diet rats with sciatic nerve crush-injury.

Cortical sensorimotor alterations classify clinical phenotype and putative genotype of spasmodic dysphonia.

BACKGROUND AND PURPOSE: Spasmodic dysphonia (SD), or laryngeal dystonia, is a task-specific isolated focal dystonia of unknown causes and pathophysiology. Although functional and structural abnormalities have been described in this disorder, the influence of its different clinical phenotypes and genotypes remains scant, making it difficult to explain SD pathophysiology and to identify potential biomarkers. METHODS: We used a combination of independent component analysis and linear discriminant analysis of resting-state functional magnetic resonance imaging data to investigate brain organization in different SD phenotypes (abductor versus adductor type) and putative genotypes (familial versus sporadic cases) and to characterize neural markers for genotype/phenotype categorization. RESULTS: We found abnormal functional connectivity within sensorimotor and frontoparietal networks in patients with SD compared with healthy individuals as well as phenotype- and genotype-distinct alterations of these networks, involving primary somatosensory, premotor and parietal cortices. The linear discriminant analysis achieved 71% accuracy classifying SD and healthy individuals using connectivity measures in the left inferior parietal and sensorimotor cortices. When categorizing between different forms of SD, the combination of measures from the left inferior parietal, premotor and right sensorimotor cortices achieved 81% discriminatory power between familial and sporadic SD cases, whereas the combination of measures from the right superior parietal, primary somatosensory and premotor cortices led to 71% accuracy in the classification of adductor and abductor SD forms. CONCLUSIONS: Our findings present the first effort to identify and categorize isolated focal dystonia based on its brain functional connectivity profile, which may have a potential impact on the future development of biomarkers for this rare disorder.

Neuroprotective activity of hydroponic Teucrium polium following bilateral ovariectomy.

Ovariectomy is known as "surgical menopause" with decreased levels of estrogen in female rodents. Its reported risks and adverse effects include cognitive impairment. The action of hydroponic Teucrium polium on nucleus basalis of Meynert (bnM) neurons following 6 weeks of ovariectomy was carried out. The analysis of spike activity was observed by on-line selection and the use of a software package. Early and late tetanic, - posttetanic potentiation and depression of neurons to high frequency stimulation of hippocampus were studied. The complex averaged peri-event time and frequency histograms were constructed. The histochemical study of the activity of Са(2+)-dependent acid phosphatase was observed. In conditions of hydroponic Teucrium polium administration, positive changes in neurons and gain of metabolism leading to cellular survival were revealed. The administration of Teucrium polium elicited neurodegenerative changes in bnM.

Afferent subcortical connections into the motor cortical larynx area in the rhesus monkey.

In three rhesus monkeys (Macaca mulatta), the inferior motor cortex was explored by electrical stimulation for sites yielding vocal fold adduction. The retrograde tracer wheat germ-agglutinin-conjugated horseradish peroxidase was injected into the effective sites. Within the forebrain, retrogradely labeled cells were found in the claustrum, basal nucleus of Meynert, substantia innominata, extended amygdala, lateral and posterior hypothalamic area, field H of Forel, and a number of thalamic nuclei with the strongest labeling in the nuclei ventralis lateralis, ventralis posteromedialis, including its parvocellular part, medialis dorsalis and centrum medianum, and weaker labeling in the nuclei ventralis anterior, ventralis posterolateralis, intermediodorsalis, paracentralis, parafascicularis and pulvinaris anterior. In the midbrain, labeling was found in the deep mesencephalic nucleus, ventral tegmental area, and substantia nigra. In the lower brainstem, labeled cells were found in the pontine reticular formation, median and dorsal raphe nuclei, medial parabrachial nucleus, and locus coeruleus. The findings are discussed in terms of the possible role of these structures in voluntary vocal control.

Afferent cortical connections of the motor cortical larynx area in the rhesus monkey.

The present study describes the cortical input into the motor cortical larynx area. The retrograde tracer horseradish peroxidase-conjugated wheat germ agglutinin was injected into the electrophysiologically identified motor cortical larynx area in three rhesus monkeys (Macaca mulatta). Retrogradely labeled cells were found in the surrounding premotor cortex (areas 6V and 6D), primary motor cortex (area 4), primary somatosensory cortex (areas 3, 1 and 2), anterior and posterior secondary somatosensory cortex and the probable homologue of Broca's area (areas 44 and 45); furthermore, labeling was found in the supplementary motor area, anterior and posterior cingulate cortex (areas 24 and 23), prefrontal and orbital frontal cortex (areas 8A, 46V, 47/12L, 47/12O, 13), agranular, dysgranular and granular insula as well as in the cortex within the upper bank of the middle third of the superior temporal sulcus (area TPO). The majority of these regions are reciprocally connected with the motor cortical larynx area [Brain Res 949 (2000) 23]. The laryngeal motor cortical input is discussed in relation to the connections of other motor cortical areas and its role in vocal control.