Daniel A. Gorman

Neural Systems Subserving Valence and Arousal During the Experience of Induced Emotions

The circumplex model of affect construes all emotions as linear combinations of 2 independent neurophysiological dimensions, valence and arousal. We used functional magnetic resonance imaging to identify the neural networks subserving valence and arousal, and we assessed, in 10 participants, the associations of the BOLD (blood oxygen level-dependent) response, an indirect index of neural activity, with ratings of valence and arousal during the emotional experiences induced by the presentation of evocative sentences. Unpleasant emotional experience was associated with increased BOLD signal intensities in the supplementary motor, anterior midcingulate, right dorsolateral prefrontal, occipito-temporal, inferior parietal, and cerebellar cortices. Highly arousing emotions were associated with increased BOLD signal intensities in the left thalamus, globus pallidus, caudate, parahippocampal gyrus, amygdala, premotor cortex, and cerebellar vermis. Separate analyses using a finite impulse response model confirmed these results and revealed that pleasant emotions engaged an additional network that included the midbrain, ventral striatum, and caudate nucleus, all portions of a reward circuit. These findings suggest the existence of distinct networks subserving the valence and arousal dimensions of emotions, with midline and medial temporal lobe structures mediating arousal and dorsal cortical areas and mesolimbic pathways mediating valence.

The Neurophysiological Bases of Emotion: An fMRI Study of the Affective Circumplex Using Emotion-Denoting Words

Objective: We aimed to study the neural processing of emotion‐denoting words based on a circumplex model of affect, which posits that all emotions can be described as a linear combination of two neurophysiological dimensions, valence and arousal. Based on the circumplex model, we predicted a linear relationship between neural activity and incremental changes in these two affective dimensions. Methods: Using functional magnetic resonance imaging, we assessed in 10 subjects the correlations of BOLD (blood oxygen level dependent) signal with ratings of valence and arousal during the presentation of emotion‐denoting words. Results: Valence ratings correlated positively with neural activity in the left insular cortex and inversely with neural activity in the right dorsolateral prefrontal and precuneus cortices. The absolute value of valence ratings (reflecting the positive and negative extremes of valence) correlated positively with neural activity in the left dorsolateral and medial prefrontal cortex (PFC), dorsal anterior cingulate cortex, posterior cingulate cortex, and right dorsal PFC, and inversely with neural activity in the left medial temporal cortex and right amygdala. Arousal ratings and neural activity correlated positively in the left parahippocampus and dorsal anterior cingulate cortex, and inversely in the left dorsolateral PFC and dorsal cerebellum. Conclusion: We found evidence for two neural networks subserving the affective dimensions of valence and arousal. These findings clarify inconsistencies from prior imaging studies of affect by suggesting that two underlying neurophysiological systems, valence and arousal, may subserve the processing of affective stimuli, consistent with the circumplex model of affect. Hum Brain Mapp, 2009.

An affective circumplex model of neural systems subserving valence, arousal, and cognitive overlay during the appraisal of emotional faces

Increasing evidence supports the existence of distinct neural systems that subserve two dimensions of affect--arousal and valence. Ten adult participants underwent functional magnetic resonance imaging during which they were presented a range of standardized faces and then asked, during the scan, to rate the emotional expressions of the faces along the dimensions of arousal and valence. Lower ratings of arousal accompanied greater activity in the amygdala complex, cerebellum, dorsal pons, and right medial prefrontal cortex (mPFC). More negative ratings of valence accompanied greater activity in the dorsal anterior cingulate (dACC) and parietal cortices. Extreme ratings of valence (highly positive and highly negative ratings) accompanied greater activity in the temporal cortex and fusiform gyrus. Building on an empirical literature which suggests that the amygdala serves as a salience and ambiguity detector, we interpret our findings as showing that a face rated as having low arousal is more ambiguous and a face rated as having extreme valence is more personally salient. This explains how both low arousal and extreme valence lead to greater activation of an ambiguity/salience system subserved by the amygdala, cerebellum, and dorsal pons. In addition, the right medial prefrontal cortex appears to down-regulate individual ratings of arousal, whereas the fusiform and related temporal cortices seem to up-regulate individual assessments of extreme valence when individual ratings are studied relative to group reference ratings for each stimulus. The simultaneous assessment of the effects of arousal and valence proved essential for the identification of neural systems contributing to the processing of emotional faces.

Canadian Guidelines for the Evidence-Based Treatment of Tic Disorders: Pharmacotherapy:

This article seeks to provide the practising clinician with guidance on the pharmacological management of tic disorders in children and adults. We performed a systematic review of the literature on the treatment of tic disorders. A multi-institutional group of 14 experts in psychiatry, child psychiatry, neurology, pediatrics, and psychology engaged in a consensus meeting. The evidence was presented and discussed, and nominal group techniques were employed to arrive at consensus on recommendations. A strong recommendation is made when the benefits of treatment clearly outweigh the risks and burdens, and can apply to most patients in most circumstances without reservation. With a weak recommendation, the benefits, risks, and burdens are more closely balanced, and the best action may differ depending on the circumstances. Based on these principles, weak recommendations were made for the use of pimozide, haloperidol, fluphenazine, metoclopramide (children only), risperidone, aripiprazole, olanzapine, quetiapine, ziprasidone, topiramate, baclofen (children only), botulinum toxin injections, tetrabenazine, and cannabinoids (adults only). Strong recommendations were made for the use of clonidine and guanfacine (children only). While the evidence supports the efficacy of many of the antipsychotics for the treatment of tics, the high rates of side effects associated with these medications resulted in only weak recommendations for these drugs. In situations where tics are not severe or disabling, the use of a medication with only a weak recommendation is not warranted. However, when tics are more distressing and interfering, the need for tic suppression to improve quality of life is stronger, and patients and clinicians may be more willing to accept the risks of pharmacotherapy.

Psychosocial outcome and psychiatric comorbidity in older adolescents with Tourette syndrome: controlled study

BACKGROUND Children with Tourette syndrome generally experience improvement of tics by age 18 years, but psychosocial and comorbidity outcomes at this age are unclear. AIMS To compare psychosocial outcomes and lifetime comorbidity rates in older adolescents with Tourette syndrome and controls. We hypothesised a priori that individuals with Tourette syndrome would have lower Childrens Global Assessment Scale (CGAS) scores. METHOD A total of 65 individuals with Tourette syndrome, identified in childhood, and 65 matched community controls without tic or obsessive-compulsive disorder (OCD) symptoms were assessed around 18 years of age regarding psychosocial functioning and lifetime psychiatric disorders. RESULTS Compared with controls, individuals with Tourette syndrome had substantially lower CGAS scores (P = 10(-8)) and higher rates of attention-deficit hyperactivity disorder (ADHD), major depression, learning disorder and conduct disorder (P< or =0.01). In the participants with Tourette syndrome, poorer psychosocial outcomes were associated with greater ADHD, OCD and tic severity. CONCLUSIONS Clinically ascertained children with Tourette syndrome typically have impaired psychosocial functioning and high comorbidity rates in late adolescence.

The natural history of microalbuminuria in adolescents with type 1 diabetes.

OBJECTIVE To describe the natural history of urinary albumin excretion measured initially during the first decade of type 1 diabetes in adolescents and to identify predictors of the onset and progression of microalbuminuria (MA) in this population. STUDY DESIGN A retrospective cohort follow-up study was done on 76 adolescents whose albumin excretion rate (AER) had been determined in the first decade of their diabetes. Subjects were monitored for a mean of 6 years after initial AER testing. Those with MA were compared with a group with similar age, sex, and diabetes duration who initially had normoalbuminuria (NA). RESULTS Of the 28 with initial MA, 9 (32%) regressed (8 to within the NA range), whereas MA was persistent in 10 (36%) and progressed in 9 (32%), 5 to overt proteinuria. Of the 47 who had initial NA, MA developed in 14 (30%) and overt proteinuria in 3 (6%). With MA status at follow-up as the dependent variable, multiple regression analysis showed that initial AER (P =.0002) and hemoglobin A1c (P =.02) measured at the same time were significant independent variables. CONCLUSIONS These data suggest that in adolescents: (1) MA detected in the first decade of disease will persist or progress in the second decade in approximately two thirds of patients, and new MA will develop in a third of those initially normoalbuminuric; and (2) the appearance, persistence, or progression of MA is influenced in large part by metabolic control assessed by hemoglobin A1c both at initial MA screening and throughout the course of diabetes. This underlines the need for MA screening starting early in the course of type 1 diabetes in adolescents and for maintenance of good metabolic control.

Canadian Guidelines for the Evidence-Based Treatment of Tic Disorders: Behavioural Therapy, Deep Brain Stimulation, and Transcranial Magnetic Stimulation:

This clinical guideline provides recommendations for nonpharmacological treatments for tic disorders. We conducted a systematic literature search for clinical trials on the treatment of tics. One evidence-based review (including 30 studies) and 3 studies on behavioural interventions, 3 studies on deep brain stimulation (DBS), and 3 studies on transcranial magnetic stimulation (TMS) met our inclusion criteria. Based on this evidence, we have made strong recommendations for the use of habit reversal therapy and exposure and response prevention, preferably embedded within a supportive, psychoeducational program, and with the option to combine either of these approaches with pharmacotherapy. Although evidence exists for the effcacy of DBS, the quality of this evidence is poor and the risks and burdens of the procedure are fnely balanced with the perceived benefts. Our recommendation is that this intervention continues to be considered an experimental treatment for severe, medically refractory tics that have imposed severe limitations on quality of life. We recommend that the procedure should only be performed within the context of research studies and by physicians expert in DBS programming and in the management of tics. There is no evidence to support the use of TMS in the treatment of tics. However, the procedure is associated with a low rate of known complications and could continue to be evaluated within research protocols. The recommendations we provide are based on current knowledge, and further studies may result in their revision in future.

Canadian guidelines on pharmacotherapy for disruptive and aggressive behaviour in children and adolescents with attention-deficit hyperactivity disorder, oppositional defiant disorder, or conduct disorder

Objective: To develop evidence-based guidelines on pharmacotherapy for severe disruptive and aggressive behaviour in children and adolescents with attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), or conduct disorder (CD). The guidelines assume that psychosocial interventions have been pursued but did not achieve sufficient improvement. Method: A multidisciplinary consensus group used the Grading of Recommendations Assessment, Development and Evaluation approach for rating evidence quality and for grading recommendations. We conducted a systematic review of medications studied in placebo-controlled trials for treating disruptive and aggressive behaviour in children and adolescents with ADHD, ODD, or CD. We followed consensus procedures to make 1 of 4 recommendations for each medication: strong, in favour (↑↑); conditional, in favour (↑?); conditional, against (↓?); and strong, against (↓↓). Results: For children and adolescents with disruptive or aggressive behaviour associated with ADHD, psychostimulants received a strong recommendation in favour of use, while atomoxetine and alpha-2 agonists received a conditional recommendation in favour of use. If these patients do poorly with ADHD medications, the medication with the most evidence is risperidone. Risperidone also has the most evidence for treating disruptive or aggressive behaviour in the absence of ADHD. However, given risperidones major adverse effects, it received only a conditional recommendation in favour of use. We recommended against using quetiapine, haloperidol, lithium, or carbamazepine because of the poor quality of evidence and their major adverse effects. Conclusion: When severe disruptive or aggressive behaviour occurs with ADHD, medications for ADHD should be used first. Other medications have major adverse effects and, with the exception of risperidone, very limited evidence to support their use.

The pharmacological management of oppositional behaviour, conduct problems, and aggression in children and adolescents with attention-deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder: a systematic review and meta-analysis. Part 2: antipsychotics and traditional mood stabilizers

Objective: Attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) are among the most common psychiatric diagnoses in childhood. Aggression and conduct problems are a major source of disability and a risk factor for poor long-term outcomes. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) of antipsychotics, lithium, and anticonvulsants for aggression and conduct problems in youth with ADHD, ODD, and CD. Each medication was given an overall quality of evidence rating based on the Grading of Recommendations Assessment, Development and Evaluation approach. Results: Eleven RCTs of antipsychotics and 7 RCTs of lithium and anticonvulsants were included. There is moderate-quality evidence that risperidone has a moderate-to-large effect on conduct problems and aggression in youth with subaverage IQ and ODD, CD, or disruptive behaviour disorder not otherwise specified, with and without ADHD, and high-quality evidence that risperidone has a moderate effect on disruptive and aggressive behaviour in youth with average IQ and ODD or CD, with and without ADHD. Evidence supporting the use of haloperidol, thioridazine, quetiapine, and lithium in aggressive youth with CD is of low or very-low quality, and evidence supporting the use of divalproex in aggressive youth with ODD or CD is of low quality. There is very-low-quality evidence that carbamazepine is no different from placebo for the management of aggression in youth with CD. Conclusion: With the exception of risperidone, the evidence to support the use of antipsychotics and mood stabilizers is of low quality.

Second-Generation Antipsychotics for the Treatment of Disruptive Behaviour Disorders in Children: A Systematic Review

Objective: The use of second-generation antipsychotics (SGAs) in youth has increased considerably. Increases are mainly attributable to treatment of disruptive behaviour disorders (DBDs). Our objective was to review the evidence regarding the efficacy of SGAs for DBDs in youth. Method: We performed a systematic review of all randomized controlled trials (RCTs) of SGAs and placebo for the treatment of DBDs in youth, focusing on efficacy data. Results: Eight RCTs in youth with DBDs were included. Five RCTs evaluated the use of risperidone in youth with the combination of subaverage-borderline IQ and disruptive behaviour-aggression. Single RCTs evaluated the use of risperidone for treatment-resistant aggression in attention-deficit hyperactivity disorder and for the treatment of conduct disorder (CD), and a single RCT evaluated the use of quetiapine for adolescent CD. The efficacy results of each of these studies are described. Conclusion: Four placebo-controlled studies support the short-term efficacy of low-dose risperidone in youth with a subaverage IQ. Placebo-controlled evidence is weak or nonexistent for SGAs other than risperidone, and is weak in youth with an average IQ. Multiple factors likely account for the disconnect between this limited evidence base and the frequent use of SGAs for DBDs in clinical practice. These include extrapolation from studies in youth with autism or a subaverage IQ to normally developing youth; ease of SGA titration and the mistaken perception that little monitoring is required; unavailability of psychosocial treatments; limited familiarity with other pharmacological options; clinical and cultural norms; and the influence of the pharmaceutical industry.