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Biomedical subjects

Ben J Harrison

Publications and source records attributed to Ben J Harrison.

14 recordsLinked to original sources
PubMed2006

Dysfunction of dorsolateral prefrontal cortex in antipsychotic-naïve schizophreniform psychosis.

Reports of abnormal activation of the dorsolateral prefrontal cortex (dlPFC) are common in functional neuroimaging studies of schizophrenia, although very few have examined brain activity in patients close to the onset of illness. In this H(2)(15)O PET study, eight young male patients with first-episode schizophreniform psychosis and age-matched control subjects performed a version of the Stroop task that we have previously shown to engage the middle-frontal gyrus. At the time of testing, patients were antipsychotic-naïve and were scanned within 1 week of initial contact with our clinical program. All patients received a later diagnosis of schizophrenia 6 months after participating in the study. Whole-brain (within-group) and region-of-interest (between-group) analyses were carried out and data underwent spatial reproducibility testing. Compared with healthy subjects, patients showed significantly greater reaction-time (RT) interference but normal RT accuracy on the Stroop task. This pattern correlated with significant under-activation of the posterior left middle-frontal gyri in the patient versus control group. These findings support an emerging model of impaired cognitive control in schizophrenia and suggest that there is significant dysfunction of the dlPFC close to the onset of illness that may coincide with, or be modulated by, the transition-to-illness phase.

Adolescent↗
PubMed2006

Evaluating brain activity in obsessive-compulsive disorder: preliminary insights from a multivariate analysis.

Obsessive-compulsive disorder (OCD) has been linked to a dysfunction of brain corticostriatal networks, although functional imaging studies of OCD rarely apply network-sensitive analysis methods. In this study, we compared a univariate and a multivariate analysis of PET data in OCD patients and healthy subjects; the latter approach was considered more suitable for characterizing functional networks of brain activity. Although both methods suggested there was abnormal corticostriatal activity in OCD patients, the nature, extent and magnitude of this activity was clearly enhanced by the multivariate approach. Implications for the analysis of such studies are discussed.

Adult↗
PubMed2005

Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans.

Functional abnormalities in muscarinic and nicotinic receptors are associated with a number of disorders including Alzheimer's disease and schizophrenia. While the contribution of muscarinic receptors in modulating cognition is well established in humans, the effects of nicotinic receptors and the interactions and possible synergistic effects between muscarinic and nicotinic receptors have not been well characterized in humans. The current study examined the effects of selective and simultaneous muscarinic and nicotinic receptor antagonism on a range of cognitive processes. The study was a double-blind, placebo-controlled, repeated measures design in which 12 healthy, young volunteers completed cognitive testing under four acute treatment conditions: placebo (P); mecamylamine (15 mg) (M); scopolamine (0.4 mg i.m.) (S); mecamylamine (15 mg)/scopolamine (0.4 mg i.m.) (MS). Muscarinic receptor antagonism with scopolamine resulted in deficits in working memory, declarative memory, sustained visual attention and psychomotor speed. Nicotinic antagonism with mecamylamine had no effect on any of the cognitive processes examined. Simultaneous antagonism of both muscarinic and nicotinic receptors with mecamylamine and scopolamine impaired all cognitive processes impaired by scopolamine and produced greater deficits than either muscarinic or nicotinic blockade alone, particularly on working memory, visual attention and psychomotor speed. These findings suggest that muscarinic and nicotinic receptors may interact functionally to have synergistic effects particularly on working memory and attention and suggests that therapeutic strategies targeting both receptor systems may be useful in improving selective cognitive processes in a number of disorders.

Adult↗
PubMed2005

Functional connectivity during Stroop task performance.

Using covariance-based multivariate analysis, we examined patterns of functional connectivity in rCBF on a practice-extended version of the Stroop color-word paradigm. Color-word congruent and incongruent conditions were presented in six AB trials to healthy subjects during 12 H2(15)O PET scans. Analyses identified two reproducible canonical eigenimages (CE) from the PET data, which were converted to a standard Z score scale after cross-validation resampling and correction for random subject effects. The first CE corresponded to practice-dependent changes in covarying rCBF that occurred over early task repetitions and correlated with improved behavioral performance. This included many regions previously implicated by PET and fMRI studies of this task, which we suggest may represent two "parallel" networks: (i) a cingulo-frontal system that was initially engaged in selecting and mapping a task-relevant response (color naming) when the attentional demands of the task were greatest; and (ii) a ventral visual processing stream whose concurrent decrease in activity represented the task-irrelevant inhibition of word reading. The second CE corresponded to a consistent paradigmatic effect of Stroop interference on covarying rCBF. Coactivations were located in dorsal and ventral prefrontal regions as well as frontopolar cortex. This pattern supports existing evidence that prefrontal regions are involved in maintaining attentional control over conflicting response systems. Taken together, these findings may be more in line with theoretical models that emphasize a role for practice in the emergence of Stroop phenomena. These findings may also provide some additional insight into the nature of anterior cingulate- and prefrontal cortical contributions to implementing cognitive control in the brain.

Arousal↗
PubMed2004

Simultaneous depletion of tryptophan, tyrosine and phenylalanine as an experimental method to probe brain monoamine function in humans.

Brain monoamines are important regulators of affective and cognitive processes and are involved in the aetiology of a number of psychiatric disorders. While methods to probe serotonin and catecholamine function are established, limited methods are available to probe monoamine function as a whole in humans. In the current study, we examined if simultaneous depletion of monoamine precursors can be used as a possible probe of monoamine function. Ten healthy subjects were tested under two treatment conditions; balanced control (B) condition and combined monoamine depletion (CMD) condition. Monoamine precursor depletion was associated with significant reductions in plasma-free tryptophan (46%), tyrosine (74%) and phenylalanine (78%). Greater reductions were achieved for ratios of each precursor to other large neutral amino acids (LNAA); tryptophan/LNAA (86%), tyrosine/LNAA (94%) and phenylalanine/LNAA (94%). Findings suggest that simultaneous depletion of monoamine precursors can achieve significant plasma monoamine depletion in the range expected to affect brain monoamine function.

Adolescent↗
PubMed2004

Selective effects of simultaneous monoamine depletion on mood and emotional responsiveness.

Monoamines play a significant role in the regulation of mood and emotion. While the selective effects of serotonin and catecholamine depletion on mood have been described, the effects of simultaneous monoamine depletion on subjective measures of mood and emotional responsiveness are yet to be examined. The current study aimed to investigate the effects of simultaneous monoamine depletion on mood and emotional responsiveness in healthy participants. Twenty female participants completed a randomized, double-blind, placebo-controlled study, under a balanced control condition (B), and a combined monoamine depletion condition (CMD; via tryptophan, tyrosine and phenylalanine depletion). Mood ratings Visual Analogue Mood Scale (VAMS) and Profile Of Mood States (POMS) and measures of emotional responsiveness (Emotional Stroop and International Affective Picture System) were examined at baseline and 5 h post-depletion. Following CMD, participants rated themselves as feeling sadder, more antagonistic, and mentally slower on three VAMS subscales. There were no significant mood changes found on the POMS or measures of emotional responsiveness. These findings suggest that simultaneous depletion of all monoamines may have selective effects on mood. The findings provide evidence that the simultaneous monoamine depletion technique may be a useful experimental method to probe central monoamine function in humans.

Adolescent↗
PubMed2004

The acute effects of L-theanine in comparison with alprazolam on anticipatory anxiety in humans.

L-Theanine (delta-glutamylethylamide) is one of the predominant amino acids ordinarily found in green tea, and historically has been used as a relaxing agent. The current study examined the acute effects of L-theanine in comparison with a standard benzodiazepine anxiolytic, alprazolam and placebo on behavioural measures of anxiety in healthy human subjects using the model of anticipatory anxiety (AA). Sixteen healthy volunteers received alprazolam (1 mg), L-theanine (200 mg) or placebo in a double-blind placebo-controlled repeated measures design. The acute effects of alprazolam and L-theanine were assessed under a relaxed and experimentally induced anxiety condition. Subjective self-reports of anxiety including BAI, VAMS, STAI state anxiety, were obtained during both task conditions at pre- and post-drug administrations. The results showed some evidence for relaxing effects of L-theanine during the baseline condition on the tranquil-troubled subscale of the VAMS. Alprazolam did not exert any anxiolytic effects in comparison with the placebo on any of the measures during the relaxed state. Neither L-theanine nor alprazalam had any significant anxiolytic effects during the experimentally induced anxiety state. The findings suggest that while L-theanine may have some relaxing effects under resting conditions, neither L-theanine not alprazolam demonstrate any acute anxiolytic effects under conditions of increased anxiety in the AA model.

Adult↗
PubMed2004

Simultaneous depletion of serotonin and catecholamines impairs sustained attention in healthy female subjects without affecting learning and memory.

Monoamine neurotransmitters, serotonin, noradrenaline and dopamine modulate many important cognitive processes such as attention, learning and memory. While the selective effects of serotonin and catecholamine depletion on such processes have been investigated, the effects of simultaneous depletion of these monoamines on cognition remain unclear. This is of particular interest given that multiple neurotransmitter abnormalities have been implicated in many psychiatric disorders. The aim of the current study was to examine the effects of lowered brain monoamine function on cognitive performance, using the technique of amino acid precursor depletion. The study was a double-blind, placebo-controlled design in which 20 healthy female subjects were tested under a combined monoamine depletion condition (CMD) and a balanced control condition (B). Cognitive testing was conducted at baseline and 5 h post-depletion. The CMD condition relative to the B condition resulted in deficits in digit vigilance (accuracy and reaction time), a measure of sustained attention. There were no effects on measures of learning and memory or psychomotor function. These findings suggest that simultaneously depleting the availability of brain serotonin and catecholamines in healthy female subjects selectively impairs sustained attention, without affecting other cognitive domains.

Adolescent↗
PubMed2004

Selective effects of acute serotonin and catecholamine depletion on memory in healthy women.

There is converging evidence that brain serotonin and dopamine may selectively modulate learning and memory in humans. However, this has not been directly demonstrated. In the current study, we used the method of amino acid precursor depletion to explore the effects of low serotonin and catecholamine function on memory in healthy female volunteers. Participants completed three experimental sessions: (i) tryptophan depletion (TD to lower 5-HT); (ii) tyrosine and phenylalanine depletion (TPD to lower catecholamines); and (iii) a balanced control condition (Bal). All testing was conducted in a double-blind, placebo-controlled, crossover design. Cognitive and mood assessments were performed at baseline and 5 h after ingesting the amino acid mixture. Consistent with previous studies, TD impaired declarative memory consolidation on a structured word-learning task, while TPD, acting to lower brain dopamine availability, impaired spatial working memory. No secondary deficits were observed on measures of attention, short-term memory or subjective mood state. These findings suggest that low brain serotonin versus dopamine selectively impairs memory performance in humans. This may shed light on the role of these neurotransmitters in disorders that are characterized by significant memory impairment.

Adult↗
PubMed2002

Effects of serotonin and catecholamine depletion on interleukin-6 activation and mood in human volunteers.

There is increasing evidence that depression and related neurotic illnesses are associated with alterations in immune function that may contribute to their pathogenesis. For example, clinical and experimental studies have shown that abnormal HPA-axis activation and monoamine neurotransmission may be related to an increased release of proinflammatory cytokines from stimulated lymphocytes in the periphery and brain. In the present investigation, the effects of tryptophan depletion (TD) on unstimulated plasma interleukin-6 (IL-6) concentrations were investigated in order to determine whether acute changes in serotonin (5-HT) neurotransmission would induce a proinflammatory response in healthy individuals. The effects of TD were compared with the analogous procedure of tyrosine depletion (TPD), which reduces catecholamine metabolism in humans. Thirteen female participants completed three experimental sessions: TD, TPD and a balanced-control condition (B). Mood-ratings and blood sampling were performed at baseline and 5 h after the administration of the mixtures. Analyses revealed that TD and TPD markedly reduced tryptophan and tyrosine/phenylalanine levels, respectively. No changes in plasma IL-6 production or ratings of lowered mood were observed, however, subjects did report feeling more fatigued after TD. These findings indicate that a transient disruption in global monoamine function does not stimulate a proinflammatory response of IL-6 in normal volunteers.

Adult↗
PubMed2002

Brain monoamines and early visual information-processing speed.

Visual inspection time (IT) is a measure of information-processing speed, which correlates reliably with psychometric intelligence. Pharmacological research into IT indicates that manipulation of the cholinergic system modulates performance on the IT task, however the contribution of other neurotransmitters to this modality remains unclear. This study was designed to examine the effects of low brain serotonin and catecholamine availability on IT using the established method of amino-acid precursor depletion. Female participants (n=13) completed three experimental sessions; tryptophan depletion (TD); tyrosine/phenylalanine depletion (TPD); and a balanced control condition (B) in a randomized, double-blind cross-over design. IT assessments were performed at baseline and approx. 5 h post-mixture administration. IT scores were unaffected by either of the treatment conditions. These findings suggest that monoamines, whilst implicated in various forms of cognition are not central to IT, which measures the efficiency of perceptual intake and information-processing speed.

Adult↗