Physiological (intracortical microstimulation) and anatomical (transport of horseradish peroxidase conjugated to wheat germ agglutinin as shown by tetramethyl benzidine) approaches were combined in the same animals to reveal the locations, extents, and cortical connections of the frontal eye fields (FEF) in squirrel, owl, and macaque monkeys. In some of the same owl and macaque monkeys, intracortical microstimulation was also used to evoke eye movements from dorsomedial frontal cortex (the supplementary motor area). In addition, in all of the owl and squirrel monkeys, intracortical microstimulation was also used to evoke body movements from the premotor and motor cortex situated between the central dimple and the FEF. These microstimulation data were directly compared to the distribution of anterogradely and retrogradely transported label resulting from injections of tracer into the FEF in each monkey. Since the injection sites were limited to the physiologically defined FEF, the demonstrated connections were solely those of the FEF. To aid in the interpretation of areal patterns of connections, the relatively smooth cortex of owl and squirrel monkeys was unfolded, flattened, and cut parallel to the flattened surface. Cortex of macaque monkeys, which has numerous deep sulci, was cut coronally.



Reciprocal connections with the ipsilateral frontal lobe were similar in all three species: dorsomedial cortex (supplementary motor area), cortex just rostral (periprincipal prefrontal cortex) to the FEF, and cortex just caudal (premotor cortex) to the FEF. In squirrel and owl monkeys, extensive reciprocal connections were made with cortex throughout the caudal half of the lateral fissure and, to a much lesser extent, cortex around the superior temporal sulcus. In macaque monkeys, only sparse connections were present with cortex of the lateral fissure, but extensive and dense connections were made with cortex throughout the caudal one-third to one-half of the superior temporal sulcus. In addition, very dense reciprocal connections were made with the cortex of the lateral, or inferior, bank of the intraparietal sulcus. Contralateral reciprocal connections in all three species were virtually limited to regions that correspond in location to the FEF and the supplementary motor area.



The results of this study reveal connections between the physiologically defined frontal eye field and cortical regions known to participate in higher order visual processing, short-term memory, multimodal, visuomotor, and skeletomotor functions. Some of the demonstrated pathways may contribute to functional interactions between oculomotor and skeletomotor systems, perhaps facilitating the planning and coordination of related eye, head, and hand movements.

Frontal eye field as defined by intracortical microstimulation in squirrel monkeys, owl monkeys, and macaque monkeys. II. Cortical connections.

To determine the prevalence of alcoholic myopathy and cardiomyopathy, we studied a group of 50 asymptomatic alcoholic men (mean age, 38.5 years) entering an outpatient treatment program. Studies performed included an assessment of muscle strength by electronic myometer, muscle biopsy, echocardiography, and radio-nuclide cardiac scanning, with comparison to healthy control subjects of similar age. The patients' mean (±SEM) daily alcohol consumption was 243± 13 g over an average of 16 years. These patients had no clinical or laboratory signs of malnutrition or electrolyte imbalance. Forty-two percent of the patients, as compared with none of the controls, had strength of less than 20 kg as measured in the deltoid muscle. Muscle-biopsy specimens from 23 patients (46 percent) had histologic evidence of myopathy. In the cardiac studies, when the alcoholic patients were compared with 20 healthy controls, the patients had a significantly lower mean ejection fraction (59 vs. 67 percent), a lower mean sho...

https://www.nejm.org/doi/pdf/10.1056/NEJM198902163200701?listPDF=true

The effects of alcoholism on skeletal and cardiac muscle.

• We matched 23 nonalcoholic male drinkers who were aged 21 to 25 years and had alcoholic close relatives (FHP) with 23 control subjects with negative family histories (FHN) for demographic characteristics and drinking and smoking histories. The subjective feelings of intoxication for the 46 men were studied on three occasions using placebo, 0.75 mL/kg of ethanol, and 1.1 mL/kg of ethanol. The FHP subjects (at elevated risk for the development of alcoholism) reported less intense feelings of subjective intoxication after drinking, especially during the two hours following the peak blood alcohol concentration (BAC). Group differences were most marked with the 0.75-mL/kg dose. The two groups did not differ significantly on their BACs nor on the expectation of how they would feel under the influence of alcohol.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=PSYCH&articleId=493418&pdfFileName=archpsyc_41_9_008.pdf

Subjective Responses to Alcohol in Sons of Alcoholics and Control Subjects

A countermanding paradigm was utilized to investigate the regulation of saccade initiation. Two rhesus monkeys were instructed to generate a saccade to a peripheral target; however, on a fraction of trials after a delay, the monkeys were signaled to inhibit saccade initiation. With short delays between the presentation of the target and the signal to inhibit saccade generation, monkeys withheld saccades to the peripheral target. As the delay of the stop signal increased, monkeys increasingly failed to withhold the saccade. The hypothesis that the generation of the saccade is determined by a race between a go and a stop process provides three explicit means of estimating the covert latency of response to the stop signal. This latency, known as stop signal reaction time, was estimated to be on average 82 ms for both monkeys. Because the stop signal latency represents the time required to exert inhibitory control over saccade production, the countermanding paradigm will be useful for studying neural mechanisms that regulate saccade initiation.

Countermanding saccades in macaque

Recurrent pregnancy loss is a distressing pregnancy disorder experienced by ~25% of women trying to conceive Recurrent pregnancy loss is defined as the failure of two or more clinically recognized pregnancies before 20-24 weeks of gestation and includes embryonic and fetal losses The diagnosis of an early pregnancy loss is relatively straightforward, although progress in predicting and preventing recurrent pregnancy loss has been hampered by a lack of standardized definitions, the uncertainties surrounding the pathogenesis and the highly variable clinical presentation The prognosis for couples with recurrent pregnancy loss is generally good, although the likelihood of a successful pregnancy depends on maternal age and the number of previous losses Recurrent pregnancy loss can be caused by chromosomal errors, anatomical uterine defects, autoimmune disorders and endometrial dysfunction Available treatments target the putative risk factors of pregnancy loss, although the effectiveness of many medical interventions is controversial Regardless of the underlying aetiology, couples require accurate information on their chances of having a baby and appropriate support should be offered to reduce the psychological burden associated with multiple miscarriages Future research must investigate the pathogenesis of recurrent pregnancy loss and evaluate novel diagnostic tests and treatments in adequately powered clinical trials

Recurrent pregnancy loss.

Genetic influences on the rate of development of ethanol tolerance and the ethanol physical withdrawal syndrome in mice.

There is now considerable evidence that unicellular organisms adapt to environmental or pharmacological agents which alter membrane fluidity by incorporating different fatty acids into the phospholipids of the cellular membranes. Two examples should suffice to illustrate the principle. Sinensky (1971) has demonstrated that E. Coli respond to increased environmental temperature by incorporating an increased proportion of saturated fatty acids into their phospholipids. Since increased temperature tends to made membranes more fluid, and the result of increasing the saturated fat content of the membrane should make it intrinsically less fluid, this can probably be regarded as an adaptive mechanism. An example of a similar mechanism in response to pharmacological manipulation is shown by the experiments of Nandini-Kishore, Kitajima and Thompson (1977) in which they demonstrated that Tetrahymena responded to the presence of a general anaesthetic, methoxyflurane, in its environment by increasing the proportion of saturated fatty acids in phospholipids. General anaesthetics are thought to act by expanding and fluidising the membrane (see Seeman, 1972) so that this response of Tetrahymena may be exactly analogous to adaptation to high environmental temperature. Ethanol, in concentrations which cause intoxicaction, has also been shown to fluidise membranes (Chin and Goldstein, 1977a) raising the possibility that tolerance to ethanol may, at least partly, be explained by an adaptation in the lipids of cell membranes.

Ethanol-Induced Alteration in Membrane Phospholipid Composition: Possible Relationship to Development of Cellular Tolerance to Ethanol

The rapid onset of functional tolerance to ethanol was studied in young adult mice of the TO Swiss and C57 Black strains. Drugs known to alter the metabolism of catecholamines and 5-hydroxytryptamine in mouse brain were without effect on the development of tolerance to ethanol. Amino-oxyacetic acid, which potentiates gamma-aminobutyric acid (GABA), slightly inhibited the development of tolerance, whereas the GABA antagonist, picrotoxin, produced a small increase in tolerance. The effects of treatments which altered synaptosomal membrane lipid composition were also investigated. Prolonged treatment of mice with diazacholesterol, an inhibitor of cholesterol synthesis, reduced the cholesterol content of synaptosomal membranes and, while not altering the initial sensitivity of mice to ethanol, prevented the subsequent development of tolerance. In contrast, feeding mice a diet rich in saturated fats throughout their lives reduced the unsaturated fat content of synaptosomal membranes and appeared to reduce the initial sensitivity of mice to ethanol. These results are consistent with our previous hypothesis that a reduction in unsaturation of synaptosomal membrane lipids underlies the rapid onset of ethanol tolerance in mice. They also provide further evidence for the suggestion that GABAnergic synapses may be particularly important in this respect.

S. J. Grieve

Papers

Genetic influences on the rate of development of ethanol tolerance and the ethanol physical withdrawal syndrome in mice.

Ethanol-Induced Alteration in Membrane Phospholipid Composition: Possible Relationship to Development of Cellular Tolerance to Ethanol

The rapid onset of functional tolerance to ethanol--role of different neurotransmitters and synaptosomal membrane lipids.