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Biomedical subjects

P B Johnson

Publications and source records attributed to P B Johnson.

At least 37 records · Page 2Linked to original sources

Relationship between neuroleptic dose and positive and negative symptoms.

The present study explored possible connections between neuroleptic dose and the positive and negative symptoms of schizophrenic patients. Zero-order correlations between medication dose as measured in CPZ equivalent units and standardized assessments of positive (hallucinations, delusions) and negative (blunted affect, poor rapport) symptoms were carried out on 28 hospitalized schizophrenics. While dose was positively related to over-all negative symptom scores as well as specific negative symptoms, no relation was found with positive scores. The discussion focused on the possibility that negative symptoms might represent medication-induced side effects and the need for further research.

Adult↗

Cortical networks for visual reaching.

The cortical anatomical substrates by which visual information may influence the frontal areas controlling reaching movements to visual targets were studied in monkeys. A reaching task was employed to characterize the arm-related regions of the frontal lobe. Injections of retrograde tracers into these physiologically defined cortical fields revealed a gradient of parallel corticocortical pathways originating in the superior parietal lobule and impinging upon different frontal regions. These results support the hypothesis that the superior parietal lobule can supply the frontal motor and premotor areas not only with the proprioceptive information but also with the visual input required for the control of reaching.

Animals↗

The value of ethnographic alcohol studies: a psychologist's perspective.

Drinking behavior has been studied by scientists from a variety of social science disciplines including anthropology, economics, sociology, and psychology. The very nature of their narrow, discipline-based training and work, however, has often prevented these scientists from appreciating each other's different methodologies and from conducting cooperative, interdisciplinary studies. In this paper, I discuss how my own experience with ethnographic alcohol studies influenced my research on drinking behavior. I then outline a research strategy that could be used to foster interdisciplinary alcohol studies.

Alcohol Drinking↗

Differential effects of adrenocorticotropic hormone on steroid hydroxylase activities in the inner and outer zones of the guinea pig adrenal cortex.

We have studied the effects of ACTH treatment on steroid hydroxylase activities in the inner (zona reticularis) and outer (zona fasciculata plus zona glomerulosa) zones of the guinea pig adrenal cortex. Animals received 5 or 10 U of ACTH daily for 6 days and enzyme activities were then assessed in isolated microsomal or mitochondrial preparations. In control animals, microsomal cytochrome P-450 concentrations were greater in the inner than outer zone, but mitochondrial P-450 levels were similar in the two zones. Microsomal 17 alpha-hydroxylase and mitochondrial 11 beta-hydroxylase activities were greater in the outer than inner zone, but microsomal 21-hydroxylase activity was greater in the inner zone. ACTH treatment decreased cytochrome P-450 concentrations in inner but not outer zone microsomes; mitochondrial P-450 levels were unaffected in both zones. ACTH caused a dose-dependent increase in inner zone 17 alpha-hydroxylase activity and decrease in 21-hydroxylase activity without affecting the activity of either enzyme in outer zone microsomes. ACTH also decreased 11 beta-hydroxylase activity in outer but not inner zone mitochondrial preparations. The net effect of ACTH treatment was to diminish the differences in steroid metabolism between the two zones. The results indicate that the effects of ACTH on steroid hydroxylase activities are both zone- and enzyme-dependent, suggesting the existence of multiple and independent regulatory mechanisms.

Adrenal Cortex↗

Visuomotor transformations underlying arm movements toward visual targets: a neural network model of cerebral cortical operations.

We propose a biologically realistic neural network that computes coordinate transformations for the command of arm reaching movements in 3-D space. This model is consistent with anatomical and physiological data on the cortical areas involved in the command of these movements. Studies of the neuronal activity in the motor (Georgopoulos et al., 1986; Schwartz et al., 1988; Caminiti et al., 1990a) and premotor (Caminiti et al., 1990b, 1991) cortices of behaving monkeys have shown that the activity of individual arm-related neurons is broadly tuned around a preferred direction of movements in 3-D space. Recent data demonstrate that in both frontal areas (Caminiti et al., 1990a,b, 1991) these cell preferred directions rotate with the initial position of the arm. Furthermore, the rotation of the population of preferred directions precisely corresponds to the rotation of the arm in space. The neural network model computes the motor command by combining the visual information about movement trajectory with the kinesthetic information concerning the orientation of the arm in space. The appropriate combination, learned by the network from spontaneous movement, can be approximated by a bilinear operation that can be interpreted as a projection of the visual information on a reference frame that rotates with the arm. This bilinear combination implies that neural circuits converging on a single neuron in the motor and premotor cortices can learn and generalize the appropriate command in a 2-D subspace but not in the whole 3-D space. However, the uniform distribution of cell preferred directions in these frontal areas can explain the computation of the correct solution by a population of cortical neurons. The model is consistent with the existing neurophysiological data and predicts how visual and somatic information can be combined in the different processing steps of the visuomotor transformation subserving visual reaching.

Animals↗

Relationship between covalent binding to microsomal protein and the destruction of adrenal cytochrome P-450 by spironolactone.

Previous investigations have demonstrated that guinea pig adrenal microsomes catalyze an NADPH-dependent activation of spironolactone (SL) resulting in the degradation of cytochrome(s) P-450 and decreases in steroidogenic enzyme activities. Studies were done to evaluate the relationship between the destruction of cytochrome P-450 and the covalent binding to microsomal protein by SL and by 7 alpha-thiospironolactone (7 alpha-thio-SL), an obligatory intermediate in the activation pathway. NADPH-dependent irreversible binding to guinea pig adrenal microsomal protein was demonstrable with 22-14C- and with 35S-labelled SL or 7 alpha-thio-SL as substrates. In the absence of NADPH, there was relatively little binding. NADPH-dependent covalent binding was not demonstrable with hepatic microsomal preparations. The amount of covalent binding to adrenal microsomes was far greater with 7 alpha-thio-SL than with SL and also greater with 35S-labelled than with 14C-labelled substrates. The latter results suggest the possibility of more than one reactive metabolite. Time-course experiments revealed a good correlation between covalent binding and P-450 destruction by SL and by 7 alpha-thio-SL. In addition, the 17 alpha-hydroxylase inhibitor, SU-10'603, and the 17 alpha-hydroxylase substrate, progesterone, prevented both the degradation of cytochrome P-450 and the NADPH-dependent covalent binding by 7 alpha-thio-SL. Reduced glutathione also decreased covalent binding but did not diminish P-450 destruction. The latter results indicate that some of the covalent binding is unrelated to the degradation of cytochrome P-450. However, all of the data are consistent with the hypothesis that 7 alpha-thio-SL is a suicide inhibitor of adrenal cytochrome P-450 and that covalent binding to protein is involved in the degradation of cytochrome P-450.

Adrenal Glands↗

Making arm movements within different parts of space: the premotor and motor cortical representation of a coordinate system for reaching to visual targets.

The activity of 156 individual arm-related neurons was studied in the premotor cortex (area 6) while monkeys made arm movements of similar directions within different parts of 3-dimensional space. This study was aimed at describing the relationship between premotor cortical cell activity and direction of arm movement and assessing the coordinate system underlying this relationship. We found that the activity of 152 (97.4%) cells varied in an orderly fashion with the direction of movement, in at least some region of the work space. Premotor cortical cells fired most for a given preferred direction and less for other directions of movement. These preferred directions covered the directional continuum in a uniform fashion across the work space. It was found that, as movements of similar directions were made within different parts of the work space, the cells' preferred directions changed their orientation. Although these changes had different magnitudes for different cells, at the population level, they followed closely the changes in orientation of the arm necessary to move the hand from one to another part of the work space. This shift of cells' preferred direction with the orientation of the arm in space has been observed with similar characteristics in the motor cortex (see Caminiti et al., 1990). In both premotor and motor cortices, neuronal movement population vectors provide a good description of movement direction. Unlike the individual cell preferred directions upon which they are based, movement population vectors did not change their spatial orientation across the work space, suggesting that they remain good predictors of movement direction regardless of the region of space in which movements are made. The firing frequency of both premotor and motor cortical neurons varied significantly with the position occupied by the hand in space. These static positional effects were observed in 88.5% of premotor and 91.8% of motor cortical cells. In a second task, monkeys made movements from differing origins to a common end point. This task was performed within 3 different parts of space and was aimed at dissociating movement direction from movement end point. It was found that in both premotor and motor cortices virtually all cells were related to the direction and not to the end point of movement. These data suggest that premotor and motor cortices use common mechanisms for coding arm movement direction. They also provide a basis for understanding the coordinate transformation required to move the hand toward visual targets in space.

Analysis of Variance↗

Shift of preferred directions of premotor cortical cells with arm movements performed across the workspace.

The activity of 156 neurons was recorded in the premotor cortex (Weinrich and Wise 1982) and in an adjoining rostral region of area 6 (area 6 DR; Barbas and Pandya 1987) while monkeys made visually-guided arm movements of similar direction within different parts of space. The activity of individual neurons varied most for a given preferred direction of movement within each part of space. These neurons (152/156, 97.4%) were labeled as directional. The spatial orientation of their preferred directions shifted in space to "follow" the rotation of the shoulder joint necessary to bring the arm into the different parts of the work-space. These results suggest that the cortical areas studied represent arm movement direction within a coordinate system rotating with the arm and where signals about the movement direction relate to the motor plan through a simple invariant relationship, that between cell preferred direction and arm orientation in space.

Animals↗

Computerized mapping system of cerebral evoked potentials.

The introduction of computerized analysis systems in the study of bioelectrical signals is enhancing the understanding of the physiological mechanisms which underlie cerebral evoked potentials (EPs) in response to externally applied stimuli. In the present study, short latency (0-50-ms) and long latency (0-500-ms) somatosensory evoked potentials (SEPs) were recorded by 32 scalp electrodes from normal and pathological subjects during median nerve stimulation. An interpolation procedure for estimating data values between the neighboring electrodes allowed the mapping of cortical activity across the scalp. Time signals were also transformed by an FFT algorithm and frequency maps obtained following the same interpolation procedure. Temporal and frequency maps were graphically displayed using color and three-dimensional plots. The usefulness of computerized topographical analysis is discussed; the time and frequency computer maps obtained from the same subjects are compared and their relative advantages are evaluated.

Adult↗

Making arm movements within different parts of space: dynamic aspects in the primate motor cortex.

The activity of 176 individual cells in the arm area of motor cortex (areas 4 and 6) was studied while monkeys made arm movements of similar direction within different parts of extrapersonal space. The behavioral paradigm used was a 3-dimensional reaction-time task aimed at dissociating the direction of movement, which remained similar across the work space, from the patterns of muscular activity and the angular joint excursions necessary to perform these movements. In agreement with other studies (Georgopoulos et al., 1982; Schwartz et al., 1988), we found that, within a given part of space, the activity of 169 (96.0%) cells studied increased most for a given preferred direction and less for other directions of movement. This change was graded in an orderly fashion. We further analyzed the orientation in space of the cells' preferred directions under the differing conditions of the task. We found that, as movements with similar trajectories were made within different parts of space, the cells' preferred directions changed spatial orientation. This change was of different magnitudes for different cells, but at the level of the population, it followed closely the changes in orientation of the arm necessary to perform the movements required by the task. Movement population vectors (Georgopoulos et al., 1983, 1986, 1988) computed from cell activity proved to be good predictors of movement direction regardless of where in space the movements were performed. These results indicate that motor cortical cells can code direction of movement in a way which is dependent on the position of the arm in space. The data are discussed in relation to the existence of mechanisms which facilitate the transformation between extrinsic and intrinsic coordinates. These transformations are necessary to perform arm movements to visual targets in space.

Animals↗

Reactions, expectancies, and college students' drinking.

This study examined the relationship between adolescent girls' drinking behavior and the expected reactions of parents and friends to this behavior. Analysis indicated that friends were expected to be generally more approving than parents of frequency and quantity of current drinking. The discussion focused on these results and their relationship to competing hypotheses about adolescents' alcohol use.

Adolescent↗

Segregation and overlap of callosal and association neurons in frontal and parietal cortices of primates: a spectral and coherency analysis.

The spatial relations between selected classes of association and callosal neurons were studied in the frontal and parietal lobes of the macaque monkey using retrogradely transported fluorescent dyes. Fast blue and nuclear yellow were injected in the left frontal (areas 4 and 6) and right posterior parietal (area 5) cortices, respectively. These injections led to the retrograde labeling, in the right frontal cortex, of callosal neurons projecting homotopically and association neurons projecting to ipsilateral area 5; in the left superior parietal lobule, of callosal neurons projecting to contralateral area 5 and association neurons projecting to the ipsilateral frontal lobe. In both frontal and parietal cortices, callosal and association neurons were located in layers III and V-VI; a few neurons were also found in layer II. The contribution of layers V-VI to the callosum was significantly higher in areas 4 and 6 than in area 5. Only a small number of neurons (less than 1%) were double labeled. Spectral analyses were used to characterize the spatial periodicities of the distributions of callosal and association neurons. In areas 4, 6, and 5, both association and callosal spectra were dominated by a strong elevation in the range of low spatial frequencies, corresponding to periodicities in cell density with a peak-to-peak distance of about 8 mm. This indicated an arrangement of these corticocortical cells in the form of bands. The latter displayed various shapes and orientations and were composed of more discrete assemblies of cell clusters of about 400-1000 microns width. Their presence was revealed in the power spectra by a small elevation in the range of high spatial frequencies. The coherency analysis assessed the degree of linear relationships for each spatial frequency, and therefore the degree of similarity, between callosal and association cell distributions, together with their phase relations. Little coherency was found in areas 4 and 6 between bands of callosal and association neurons, which suggests that the 2 cell populations are differently and independently distributed in the tangential domain, with no simple phase relations. The overall mean coherency was higher in area 5 than in the frontal cortex: callosal and association bands were more similar in shape, with more extensive zones of overlap. These data indicate that callosal and association neurons share common principles of spatial organization despite the great regional variability of their interrelations in the tangential cortical domain.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Callosal and association neurons in the cortical space: a spectral analysis approach.

The tangential distributions of callosal neurons of area 5 projecting homotopically to the contralateral hemisphere and of association neurons of areas 4 and 6 projecting to ipsilateral area 5 were determined in the macaque monkey by using neuroanatomical methods based on the retrograde transport of horseradish peroxidase. Both distributions were studied qualitatively through 2-dimensional reconstructions of the cortical areas of origin and quantitatively through a spectral analysis. This approach facilitated the characterization of the spatial periodicities contained in these distributions revealing that, in area 5, callosal neurons were organized in bands of various shapes and width; these bands were composed of more discrete clusters of cells. In the frontal lobe, association neurons projecting to ipsilateral area 5 were arranged similarly. This study suggests that a common principle underlies the tangential organization of both callosal and association projecting cells in different cortical areas and emphasizes a basic similarity of interhemispheric and intrahemispheric connections.

Animals↗

Effects of cadmium in vitro on microsomal steroid metabolism in the inner and outer zones of the guinea pig adrenal cortex.

Studies were carried out to evaluate the effects of cadmium in vitro on microsomal steroid metabolism in the inner (zona reticularis) and outer (zona fasciculata and zona glomerulosa) zones of the guinea pig adrenal cortex. Microsomes from the inner zone have greater 21-hydroxylase than 17 alpha-hydroxylase activity, resulting in the conversion of progesterone primarily to 11-deoxycorticosterone and of 17 alpha-hydroxyprogesterone principally to its 21-hydroxylated metabolite, 11-deoxycortisol. Microsomes from the outer zones, by contrast, have far greater 17 alpha-hydroxylase and C17,20-lyase activities than 21-hydroxylase activity. As a result, progesterone is converted primarily to its 17-hydroxylated metabolite, 17 alpha-hydroxyprogesterone; and 17 alpha-hydroxyprogesterone is converted principally to delta 4-androstenedione, with only small amounts of 21-hydroxylated metabolites being produced. Addition of cadmium to incubations with inner zone microsomes causes concentration-dependent decreases in 21-hydroxylation and increases in 17 alpha-hydroxylase and C17,20-lyase activities, resulting in a pattern of steroid metabolism similar to that in normal outer zone microsomes. Cadmium similarly decreases 21-hydroxylation by outer zone microsomes but has no effect on the formation of 17-hydroxylated metabolites or on androgen (delta 4-androstenedione) production. In neither inner nor outer zone microsomes did cadmium affect cytochrome P-450 concentrations, steroid interactions with cytochrome(s) P-450, or NADPH-cytochrome P-450 reductase activities. The results indicate that cadmium produces both quantitative and qualitative changes in adrenal microsomal steroid metabolism and that the nature of the changes differs in the inner and outer adrenocortical zones. In inner zone microsomes, there appears to be a reciprocal relationship between 21-hydroxylase and 17 alpha-hydroxylase/C17,20-lyase activities which may influence the physiological function(s) of that zone.

Adrenal Cortex↗

Maintenance of induced muscle tension, stimulus generalization performance, and schizophrenia.

Hand-dynamometer induced muscle tension was manipulated in the context of an experimental paradigm that included tests of discrimination and generalization with rigorously defined schizophrenic and affective patients, as well as schizotypic and normal controls (total N = 44). The experiment was designed to test predictions that derive from Broen and Storms' (1967) learning/motivational analysis of schizophrenic performance deficits. The results failed to support the theoretical predictions, but did reveal that the ability to maintain induced muscle tension within prescribed limits discriminated reliably between the groups (p less than or equal to .03) and that this discriminability increased with increasing tension demands (p less than or equal to .001). The data are discussed in terms of possible relations to basic sensory/motor (i.e., neuromuscular and/or proprioceptive) mechanisms as well as to more central psychological (i.e., attentional/cognitive) mechanisms, and directions for future research are outlined.

Adult↗