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Biomedical subjects

R D Rogers

Publications and source records attributed to R D Rogers.

At least 19 recordsLinked to original sources

The acute effect of alcohol on decision making in social drinkers.

RATIONALE: Many studies have reported the long-term adverse effects of alcohol on executive cognitive function in chronic alcohol abusers, yet little research has investigated the acute effects of alcohol in social drinkers. Studies on acute effects report alcohol-induced deficits on tasks that require executive cognitive processes, with alcohol acting to increase preservative errors and reduce planning. AIM: The present investigation examines the acute effects of a moderate dose of alcohol on a decision-making task that involves participants making a forced choice between two simultaneously presented binary-outcome gambles. METHODS: Alcohol (0.6 g/kg) or placebo was administered to 32 social drinkers. Participants completed the task, making a total of 80 decisions about gambles that varied in the magnitude of expected gains, losses and the probability with which these outcomes were delivered. Participants also chose between gambles probing identified non-normative biases in human decision making, namely, risk aversion for choosing between gains and risk seeking for choosing between losses. RESULTS: All participants picked the experimental gamble more frequently when the probability of winning was high vs low, when the gains were large vs small and when the losses were small vs large; the alcohol group had an impaired ability to factor in the magnitude of gains and the likelihood of winning when the losses were large. Deliberation time did not differ between the groups. CONCLUSION: These data suggest that alcohol given acutely impairs risky decision making. In particular, alcohol impairs one's ability to alter responding in light of changing prospective rewards in order to make favourable decisions.

Adult↗

The effects of a branched chain amino acid mixture supplemented with tryptophan on biochemical indices of neurotransmitter function and decision-making.

RATIONALE: We have previously shown that a 60-g mixture of branched chain amino acids (BCAAs) lowers the plasma availability of the catecholamine precursors tyrosine (TYR) and phenylalanine (PHE) and produces biochemical and neuropsychological changes consistent with impaired dopamine neurotransmission. However, the BCAA mixture also lowers the ratio of tryptophan (TRP) to BCAA which could impair brain serotonin function. OBJECTIVES: To determine the biochemical and neuropsychological effects of a BCAA mixture supplemented with TRP. METHODS: We studied 32 healthy volunteers who were randomly and blindly allocated to either a single administration of amino acid mixture (60 g BCAA and 2 g TRP) or placebo. We carried out venous sampling to measure plasma levels of amino acids and performed selected cognitive tasks sensitive to monoamine manipulation 5 h after mixture ingestion. RESULTS: Relative to placebo, the BCAA/TRP mixture substantially lowered the ratio of TYR+PHE:BCAA and increased plasma prolactin. The ratio of TRP:BCAA was also lowered but to a lesser extent. The BCAA/TRP mixture produced significant changes in a task of decision-making where volunteers showed reduced discrimination between gambles with large and small losses. CONCLUSIONS: A 62 g BCAA/TRP mixture decreases the availability of TYR and PHE for brain catecholamine synthesis and increases plasma prolactin consistent with lowered brain dopamine function. Addition of 2 g TRP to the 60 g BCAA mixture does not prevent a reduction of the ratio TRP:BCAA relative to placebo. The effects of the BCAA/TRP mixture on decision-making suggest a general action of dopamine pathways on the processing of emotional information in risky choice, including punishment-related cues, consistent with suggestions that dopamine mechanisms mediate behavioural responses to aversive as well as appetitive stimuli in instrumental conditioning.

Adult↗

Effects of beta-adrenoceptor blockade on components of human decision-making.

RATIONALE: Converging evidence from studies with neurological patients and brain imaging studies with healthy volunteers suggests that the capacity to make choices between actions associated with probabilistic rewards and punishments depends upon a network of cortico-limbic systems including the orbitofrontal cortex, cingulate cortex, amygdala and striatum. The involvement of such structures highlights the emotional aspects of decision-making and suggests that decision-making may be sensitive to manipulations of the catecholamine systems that innervate these structures. In this study, we investigated the possible role of noradrenaline (NA). OBJECTIVE: We examined the effects of a single oral 80 mg dose of the beta-adrenoceptor blocker, propranolol, on the decision-making of healthy volunteers in a double-blind, placebo-controlled, between-subjects design. METHODS: Seventeen volunteers ingested a placebo while 15 volunteers ingested propranolol. Visual analogue scales, and self-reported positive and negative ratings, were used to assess subjective changes and mood. Vital signs were also monitored. Seventy-five minutes after treatment, volunteers were asked to make a series of choices between two simultaneously presented gambles, differing in the magnitude of possible gains (i.e. reward), the magnitude of possible losses (i.e. punishment), and the probabilities with which these outcomes were delivered. Volunteers also chose between gambles probing identified non-cognitive biases in human decision-making, namely, risk-aversion when choosing between gains and risk-seeking when choosing between losses. RESULTS: Propranolol treatment did not result in gross changes in subjective state or mood in comparison to placebo, but did slow heart rate significantly. Propranolol produced a selective change in volunteers' decision-making; namely, it significantly reduced the discrimination between large and small possible losses when the probability of winning was relatively low and the probability of losing was high. CONCLUSIONS: These results suggest that NA modulates the processing of punishment signals when choosing between probabilistic rewards and punishments under conditions of increased arousal.

Adolescent↗

Willed action and attention to the selection of action.

Actions are said to be 'willed' if we consciously pay attention to their selection. It has been suggested that they are associated with activations in the dorsal prefrontal cortex (area 46). However, because previous experiments typically used a 'free selection' paradigm to examine this hypothesis, it is unclear whether the results reflected the attention to the selection of action or the freedom of choice allowed by the tasks. In this experiment, we minimized the difference of working memory demand across task conditions by using novel stimuli in each trial. We found that activation in the dorsal prefrontal cortex on a free selection task was not significantly different from that induced by another task that required attention to the selection of action, although the responses were externally specified. This suggests that the dorsal prefrontal cortex is in fact associated with attention to the selection of action, but does not play a unique role in the generation of internally initiated actions. However, the presupplementary motor area (pre-SMA) may subserve this function as activity in this region was found to be tightly associated with the free selection of responses.

Adult↗

Tryptophan depletion decreases the recognition of fear in female volunteers.

RATIONALE: Serotonergic processes have been implicated in the modulation of fear conditioning in humans, postulated to occur at the level of the amygdala. The processing of other fear-relevant cues, such as facial expressions, has also been associated with amygdala function, but an effect of serotonin depletion on these processes has not been assessed. OBJECTIVE: The present study investigated the effects of reducing serotonin function, using acute tryptophan depletion, on the recognition of basic facial expressions of emotions in healthy male and female volunteers. METHODS: A double-blind between-groups design was used, with volunteers being randomly allocated to receive an amino acid drink specifically lacking tryptophan or a control mixture containing a balanced mixture of these amino acids. Participants were given a facial expression recognition task 5 h after drink administration. This task featured examples of six basic emotions (fear, anger, disgust, surprise, sadness and happiness) that had been morphed between each full emotion and neutral in 10% steps. As a control, volunteers were given a famous face classification task matched in terms of response selection and difficulty level. RESULTS: Tryptophan depletion significantly impaired the recognition of fearful facial expressions in female, but not male, volunteers. This was specific since recognition of other basic emotions was comparable in the two groups. There was also no effect of tryptophan depletion on the classification of famous faces or on subjective state ratings of mood or anxiety. CONCLUSIONS: These results confirm a role for serotonin in the processing of fear related cues, and in line with previous findings also suggest greater effects of tryptophan depletion in female volunteers. Although acute tryptophan depletion does not typically affect mood in healthy subjects, the present results suggest that subtle changes in the processing of emotional material may occur with this manipulation of serotonin function.

Adult↗

Decision making deficits in patients with first-episode and chronic schizophrenia.

A considerable body of evidence suggests that the dorsolateral prefrontal cortex is dysfunctional in schizophrenia. However, relatively few studies have explored the involvement of other areas of the frontal cortex. Research suggests that the orbitofrontal cortex (OFC) plays an important role in decision making processes. We assessed the decision making cognition of first-episode and chronic schizophrenic patients with a novel task sensitive to orbitofrontal dysfunction. Both first-episode and chronic patients with schizophrenia took longer than matched controls to make decisions, and both groups were also impaired on a measure of risk adjustment. The impairment in these measures was more severe in the chronic patients than in the first-episode patients, and only the chronic patients made significantly fewer optimal decisions than controls. These results contribute to increasing evidence of orbitofrontal dysfunction in schizophrenia, and suggest that disease progression or the effects of long term antipsychotic medication may influence performance on this task.

Analysis of Variance↗

Neurocognitive deficits in decision-making and planning of patients with DSM-III-R borderline personality disorder.

BACKGROUND: Repeated, self-damaging behaviour occurring in the context of borderline personality disorder (BPD) may reflect impairments in decision-making and planning cognition. However, there has been no systematic neuropsychological examination of these particular cognitive functions in patients diagnosed with BPD. Such investigations may improve our understanding of the possible role of brain dysfunction in BPD and improve the characterization of the psychological difficulties associated with this disorder. METHOD: Forty-two psychiatric patients with a diagnosis of DSM-III-R BPD (41 of whom gave a history of self-harm), without a history of specified 'psychoses' or current major affective disorder, were clinically assessed before completing computerized tasks of decision-making and planning previously shown to be sensitive to frontal lobe dysfunction, and tests of spatial and pattern visual recognition memory previously shown to be sensitive to frontal lobe damage and temporal lobe damage respectively. The performance of the BPD patient group was compared with that of a non-clinical control group consisting of 42 subjects. RESULTS: The performance of the BPD patients on the decision-making task was characterized by a pattern of delayed and maladaptive choices when choosing between competing actions, and by impulsive, disinhibited responding when gambling on the outcome of their decisions. BPD patients also showed impairments on the planning task. There was no evidence of impaired visual recognition memory. Additional analyses suggested only limited effects of current medication and history of previous substance use disorder. CONCLUSIONS: These findings suggest that BPD is associated with complex impairments in dissociable cognitive processes mediated by circuitry encompassing the frontal lobes. These impairments may mediate some of the behavioural changes evident in BPD. Further work is needed to examine the specificity of these findings.

Adolescent↗

Novel cytotoxic chelators that bind iron(II) selectively over zinc(II) under aqueous aerobic conditions.

To achieve cellular iron deprivation by chelation, it is important to develop chelators with selective metal-binding properties. Selectivity for iron has long been the province of certain oxygen-donor chelators such as desferrioxamine, which target Fe(III) and exploit the strength of a relatively ionic Fe(III)-O interaction. We have been studying novel chelators that possess mechanisms to selectively chelate +2 biometals, particularly tachpyr [N,N',N"-tris(2-pyridylmethyl)-1,3,5-cis,cis-triaminocyclohexane] and derivatives from N,N',N"-trialkylation and pyridine ring alkylation. Metal-exchange and metal-binding competition reactions have been conducted at pH 7.4, 37 degrees C and time periods until no further change was observed (generally 24-48 h). Under anaerobic conditions, tachpyr is strongly selective for iron, binding 95+/-5% Fe(II) versus 5+/-5% Zn(II) in the forms [Fe(tachpyr)](2+) and [Zn(tachpyr)](2+) respectively. Under aerobic conditions, tachpyr complexes Fe(II) more effectively than Fe(III), forming iminopyridyl complexes [Fe(tachpyr-ox-n)](2+) (n=2, 4) by O(2)-induced and iron-mediated oxidative dehydrogenation. Complexes [Fe(tachpyr-ox-n)](2+) are also strongly bound forms of iron that are unaffected by an excess of Zn(II) (75 mol zinc:1 mol iron complex). The preference of tachpyr for iron over zinc under aerobic conditions appears to be hindered by oxidation of Fe(II) to Fe(III), such that the proportions bound are 44+/-10% Fe(II) versus 56+/-10% Zn(II), in the respective forms [Fe(tachpyr-ox-n)](2+) and [Zn(tachpyr)](2+). However, upon addition of the reducing agent Na(2)S(2)O(4) that converts Fe(III) to Fe(II), the binding proportions shift to 76+/-10% Fe(II) versus 24+/-10% Zn(II), demonstrating a clear preference of tachpyr for Fe(II) over Zn(II). Iron(II) is in the low-spin state in [Fe(tachpyr)](2+) and [Fe(tachpyr-ox-n)](2+) (n=2, 4), which is a likely cause of the observed selectivity. N-methylation of tachpyr [giving (N-methyl)(3)tachpyr] results in the loss of selectivity for Fe(II), which is attributed to the steric effect of the methyl groups and a resulting high-spin state of Fe(II) in [Fe(N-methyl)(3)tachpyr)](2+). The relationship of chelator selectivity to cytotoxicity in the tach family will be discussed.

Aerobiosis↗

Hydrophobic ionic liquids incorporating N-alkylisoquinolinium cations and their utilization in liquid-liquid separations.

The first examples of Room Temperature Ionic Liquids (RTIL) containing fused polycyclic N-alkylisoquinolinium cations ([Cnisoq]+) in combination with the bis(perfluoroethylsulfonyl)imide anion ([BETI]-) have been synthesized, characterized, and utilized in liquid-liquid partitioning from water; these salts have unexpectedly low melting points and give high distribution ratios for aromatic solutes, especially chlorobenzenes, between the RTIL and water.

Journal Article↗

Solvation of 1-butyl-3-methylimidazolium hexafluorophosphate in aqueous ethanol--a green solution for dissolving 'hydrophobic' ionic liquids.

The relatively hydrophobic ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate has been found to be totally miscible with aqueous ethanol between 0.5 and 0.9 mol fraction ethanol, whereas the ionic liquid is only partially miscible with either pure water or absolute ethanol; the ability to dissolve 1-butyl-3-methylimidazolium hexafluorophosphate in a 'green' aqueous solvent system has important implications for cleaning, purification, and separations using ionic liquids.

Journal Article↗

Copper(II) complexes of novel N-alkylated derivatives of cis,cis-1,3,5-triaminocyclohexane. 1. Preparation and structure.

Novel N,N',N' '-trialkylated derivatives of cis,cis-1,3,5-triaminocyclohexane (tach), designated tach-R(3), were prepared through alkylation of N-protected tach with subsequent acid deprotection, to afford N-methyl, N-ethyl, and N-n-propyl derivatives as their trihydrobromide salts. The tach-neopentyl(3) and tach-furan(3) derivatives were prepared by formation of the imine from tach and pivaldehyde or furan-2-carboxaldehyde, respectively, followed by reduction of the imine. Complexes [Cu(tach-R(3))Cl(2)] (R = Me, Et, n-Pr, CH(2)-2-thienyl, and CH(2)-2-furanyl) were prepared from CuCl(2) in MeOH or MeOH-Et(2)O solvent. Crystallographic characterization of [Cu(tach-Et(3))Br(0.8)Cl(1.2)] (Pnma, a = 8.2265(1) A, b = 12.5313(1) A, c = 15.3587(3) A, Z = 4) reveals a square-based pyramidal CuN(3)X(2) coordination sphere in which one nitrogen donor occupies the apical position at a slightly longer distance (Cu-N = 2.218(5) A) than those of the basal nitrogens (Cu-N = 2.053(2) A). The solution-phase (pH 7.4 buffered and methanol) and solid-phase structures of [Cu(tach-R(3))Cl(2)] have been studied extensively by EPR and visible-near-IR spectroscopies. The square-based pyramidal structure is retained in solution, according to correspondence of solution and solid-state data. In aqueous solution, halide is replaced by water, as indicated by the high-energy UV-vis spectral shifts and bonding parameters of [Cu(tach-Et(3))](2+)(aq) derived from EPR data. The proposed aqueous-phase species, in the pH range 7.4 to 10.1, is [Cu(tach-Et(3))(H(2)O)(2)](2+). The complex [Cu(tach-Me(3))](2+)(aq) does not appear to dimerize or form metal-hydroxo species at pH 7.4, in contrast to other Cu(II)-triamine complexes, e.g., [Cu(1,4,7-triazacyclononane)](2+) (aq) and [Cu(tach-H(3))](2+)(aq) (the complex of unalkylated tach). This difference is attributed to the steric effect of the N-alkyl groups in the tach-R(3) series.

Alkylation↗

A refinement of the biofilm formation method for waste forms stability evaluation.

A refinement of the biofilm formation method for waste form stability evaluation was carried out in this study. Refinement of the biofilm formation method became necessary because of the reduced contrast in degradation between control and experimental samples. The reduction in contrast was occasioned by the long duration of exposure (12 days) of the control samples to sterile medium of low pH in the first stage. Results of evaluation carried out reveal that the duration of the first stage of the biofilm formation method can be reduced to 24 h, with substantial increase in the contrast between degradations experienced by control and experimental samples. Reduction of the first stage can be done without compromising the efficiency of the inoculation process, which the longer duration of the first stage was originally intended to ensure. A doubt as to actual formation of biofilms on experimental samples, resulting from the use of non-sterile tubings and glass wares in the second stage, was also addressed in this study. Results reveal that substantial attachment of microbes occur on the surfaces of experimental samples in the first stage, thus any supply of microbes via the tubings and glass wares in the second stage is only additional and inconsequential.

Acidithiobacillus thiooxidans↗

Syntheses and characterizations of metal complexes derived from cis,cis-1,3,5-triaminocyclohexane-N,N',N"-triacetic acid.

A convenient six-step procedure is developed to routinely prepare the hexadentate ligand cis,cis-1,3,5-triaminocyclohexane-N,N',N"-triacetic acid (H3tachta) as an HCl salt. Complexes of gallium(III) and indium(III), [Ga(tachta)] and [In(tachta)], are synthesized from the reactions of the ligand and the corresponding metal precursors. Copper(II), palladium(II), and cobalt(II) complexes, [Cu(Htachta)], [Pd(Htachta)], and [Co(Htachta)], are obtained from the reactions of H3tachta with the corresponding metal chlorides. The structures of H3tachta.3HCl.2H2O (C12H28Cl3N3O8) and [Ga(tachta)] (C12H18GaN3O6) are characterized. The crystal of H3tachta.3HCl.2H2O is monoclinic, of the space group P2(1)/c, with a = 15.1688(4) A, b = 8.4708(2) A, c = 15.9408(2) A, beta = 108.058(1) degrees, and Z = 4; that of [Ga(tachta)] is cubic, of space group Pa3, with a = 14.0762(1) A and Z = 8. The gallium atom of [Ga(tachta)] is six-coordinated in the solid state, and the complex assumes a pseudooctahedronal geometry with the completely deprotonated hexadentate ligand encapsulating the metal ion.

Crystallography, X-Ray↗

Acute dietary tryptophan depletion impairs maintenance of "affective set" and delayed visual recognition in healthy volunteers.

RATIONALE: Altered serotonergic transmission in affective disorders and Alzheimer's disease has prompted research aimed at defining the precise cognitive effects of depleting central serotonin in humans, using acute dietary tryptophan depletion. OBJECTIVE: We examined the effects of tryptophan depletion on mood and cognition in healthy volunteers. Cognitive tests of memory and attentional processing were employed to test hypotheses of central 5-hydroxytryptamine (5-HT) function related to cortical processing. METHODS: A double-blind, parallel design, placebo control study was employed with 15 subjects in each group. Mood rating scales were performed at the start and 5 h after ingestion of the drink. Cognitive tests were also performed at 5 h, after completion of the subjective rating scales. RESULTS: A robust reduction in total tryptophan was achieved in the test group. Subjects receiving the placebo drink showed the expected effect of shift on the affective shifting task, that is, more errors in the more difficult shift versus the non-shift condition. The tryptophan-depleted group made a similar number of errors in the shift trials but failed to reduce the number of errors in the non-shift trials. The tryptophan-depleted group showed a significant impairment on the delayed pattern recognition task. No significant effects on the subjective mood measures were found. CONCLUSIONS: Tryptophan depletion abolished the normal tendency to improve error scores on non-shift trials in response to affective cues on a go/no-go task. We suggest that this inability to "maintain set" in the non-shift condition may be due to a disruption of semantic retrieval processes concerned with affect. The novel finding of impairment on a delayed visual pattern recognition task confirms and extends previous studies where selective effects on memory and learning have been found following acute tryptophan depletion.

Adult↗

Investigating the neurocognitive deficits associated with chronic drug misuse.

Cognitive deficits associated with the chronic abuse of drugs have important theoretical and clinical significance: such deficits reflect changes to the underlying cortical, sub-cortical and neuromodulatory mechanisms that underpin cognition, and also interfere directly with rehabilitative programs. Recent investigations have been made into the neuropsychology of chronic abuse of cannabis, stimulants and opiates. It is suggested that future progress in this area, involving developing advances in brain-imaging and neuropharmacology, will capitalize on experimental demonstrations of specific patterns of impairments in decision-making, attention and memory function.

Animals↗

Decision-making cognition in mania and depression.

BACKGROUND: Despite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. Recent work has suggested that differences may emerge on cognitive tasks requiring affective processing, such as decision-making. The present study sought to compare decision-making cognition in mania and depression in order to clarify the current profiles of impairment for these disorders and to contribute to our more general understanding of the relationship between mood and cognition. METHODS: Medicated manic patients, depressed patients, and normal healthy controls completed a computerized decision-making task. All subjects were asked to win as many points as possible by choosing outcomes based on variably-weighted probabilities and by placing 'bets' on each decision. RESULTS: Both patient groups were impaired on this task, as evidenced by slower deliberation times, a failure to accumulate as many points as controls and suboptimal betting strategies. Manic, but not depressed, patients made suboptimal decisions--an impairment that correlated with the severity of their illness. CONCLUSIONS: These findings are consistent with a growing consensus that manic and depressed patients are characterized by significant impairments in cognitive and particularly executive, functioning. Furthermore, the distinct patterns of observed impairment in manic and depressed patients suggests that the nature and extent of cognitive impairment differ between these two groups. Viewed in the context of other recent studies, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.

Adult↗

Lesions of the medial and lateral striatum in the rat produce differential deficits in attentional performance.

Excitotoxic lesions of the medial frontal cortex and anterior cingulate cortex in rats have been shown to produce dissociable impairments on a reaction time visual attention (5-choice) task. Because these cortical areas project to the medial striatal region, the authors predicted similar deficits after lesions of this striatal area compared with the lateral area. Compared with sham-operated controls, rats with quinolinic acid-induced medial striatal lesions showed all the behavioral changes associated with medial frontal cortex and anterior cingulate cortex lesions. In contrast, lateral striatal lesions produced profound disturbances in the performance of the task. Control tests showed little evidence of gross deficits in either group of rats in terms of motivation, locomotor function, or Pavlovian appetitive conditioning. These data suggest that the medial and lateral striatum have contrasting roles in the control of instrumental responding related to the primary sources of their cortical innervation.

Animals↗

Decision-making in mania: a PET study.

Poor decision-making is often observed clinically in the manic syndrome. In normal volunteers, decision-making has been associated with activation in the ventral prefrontal cortex and the anterior cingulate gyrus. The aim of this study was to evaluate task-related activation in bipolar manic patients in these regions of the prefrontal cortex using PET. Six subjects with mania, 10 controls and six subjects with unipolar depression (an affective patient control group) were scanned using the bolus H(2)(15)O method while they were performing a decision-making task. Activations associated with the decision-making task were observed at two levels of difficulty. Task-related activation was increased in the manic patients compared with the control patients in the left dorsal anterior cingulate [Brodmann area (BA) 32] but decreased in the right frontal polar region (BA 10). In addition, controls showed greater task-related activation in the inferior frontal gyrus (BA 47) than manic patients. A positive correlation (r(s) = 0.88) between task-related activation in the anterior cingulate and increasing severity of manic symptoms was found. Depressed patients did not show significant task-related differences in activation compared with control subjects in the regions of interest. In conclusion, these patterns of activation point to abnormal task-related responses in specific frontal regions in manic patients. Moreover, they are consistent with neuropsychological observations in patients with lesions in the ventromedial prefrontal cortex, who show similar difficulties with decision-making and provide early evidence for context-specific neural correlates of mania.

Adult↗