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Objective To describe adult outcome of people with attention-deficit/hyperactivity disorder (ADHD) diagnosed in childhood and its several key predictors via a review of 7 North American controlled prospective follow-up studies: Montreal, New York, Milwaukee, Pittsburgh, Massachusetts General Hospital (MGH), Berkeley, and 7-site Multimodal Treatment Study of Children With ADHD (MTA). Method All studies were prospective and followed children with a diagnosis of ADHD and an age- and gender-matched control group at regular intervals from childhood (6–12 years of age) through adolescence into adulthood (20–40 years of age), evaluating symptom and syndrome persistence, functional outcomes, and predictors of these outcomes. Results The rates of ADHD syndrome persistence ranged from 5.7% to 77%, likely owing to varying diagnostic criteria and the source of information (self-report vs informant report) across the studies. However, all studies observed high rates of symptomatic persistence ranging from 60% to 86%. The 7 studies were largely consistent in finding that relative to control groups, research participants with childhood-diagnosed ADHD had significant impairments in the areas of educational functioning, occupational functioning, mental health, and physical health as well as higher rates of substance misuse, antisocial behavior, and unsafe driving. The most consistently observed predictors of functional outcomes included ADHD persistence and comorbidity, especially with disruptive behavior disorders. Conclusion Childhood ADHD has high rates of symptomatic persistence, which is associated with negative functional outcomes. Characteristics that predict these negative outcomes, such as comorbid disruptive behavior disorders, may be important targets for intervention.

To determine the significance of antibodies to the phosphatidylserine/prothrombin complex (aPS/PT) in patients with systemic lupus erythematosus (SLE) antiphospholipid syndrome (APS).A total of 190 patients were included in the study: 123 (64.7%) with reliable SLE and 55 (29%) with PAPS. The control group included 100 relatively healthy subjects of comparable age. All patients were tested for classical aPL as well as IgG/IgM-anti-PS/PT by enzyme immunoassay.Based on the average values of IgG/IgM aPS/PT of the control group, the levels of positivity were allocated mean (M) + 3 or 5 standard deviations (SD): M+3SD and M+5SD. IgG aPS/PT levels above 73.6 U/ml (M+5SD) were more accurate diagnostic, for IgM aPS/PT above 18.0 U/ml. IgG-aPS/PT were detected in 84 (44%) of 190 patients. Levels above diagnostic levels were detected in 68 (65%) of 104 patients with APS (55 with PAPS and 59 with SLE+APS). Thrombosis was significantly more common in patients with IgG aPS/PT compared with patients negative for IgG aPS/PT. Arterial but not venous thrombosis was associated with IgG aPS/PT positivity.The frequency of detection of IgG aPS/PT in the examined patients was 44%, IgM aPS/PT 29% and their combination 19% of 190 patients. Half of the patients with probable APS had positive IgG aPS/PT and third IgM aPS/PT. Median IgG aPS/PT were significantly higher in patients with APS compared to patients without APS and the control group. Thrombosis was associated with IgG aPS/PT. Arterial thrombosis was significantly more frequently reported in patients with IgG aPS/PT. The sensitivity of IgG aPS/PT for reliable APS at levels greater than 73.6 units/ml was 59%, specificity 92%, for IgM aPS/PT 35% and 91%, respectively.Цель. Определить значение антител к комплексу фосфатидилсерин/протромбин (анти-ФС/ПТ) у пациентов с системной красной волчанкой (СКВ) и антифосфолипидным синдромом (АФС). Материалы и методы. В исследование включены 190 пациентов: 123 (64,7%) с достоверной СКВ и 55 (29%) с первичным АФС. Контрольную группы оставили 100 относительно здоровых человек, сопоставимых по возрасту. Всем пациентам исследовались классические антифосфолипидные антитела, а также иммуноглобулин (Ig)G/IgM-анти-ФС/ПТ иммуноферментным анализом. Результаты. На основании средних значений IgG/IgM-анти-ФС/ПТ группы контроля выделены уровни позитивности среднее арифметическое (М) + 3 или 5 стандартных отклонений (SD): М+3SD и М+5SD. Уровни IgG-анти-ФС/ПТ выше 73,6 Ед/мл (M+5SD) диагностически более точные, для IgМ-анти-ФС/ПТ выше 18,0 Ед/мл. IgG-анти-ФС/ПТ выявлены у 84 (44%) из 190 пациентов. Уровни выше диагностических выявлялись у 68 (65%) из 104 пациентов с АФС (55 с первичным АФС и 59 с СКВ+АФС). Тромбозы достоверно чаще отмечались у пациентов с IgG-анти-ФС/ПТ по сравнению с пациентами, негативными по IgG-анти-ФС/ПТ. Артериальные, но не венозные тромбозы ассоциировались с позитивностью по IgG-анти-ФС/ПТ. Заключение. Частота выявления IgG-анти-ФС/ПТ у обследованных пациентов составила 44%, IgМ-анти-ФС/ПТ 29% и их сочетание 19% из 190 больных. Медиана уровней IgG-анти-ФС/ПТ достоверно выше у пациентов с АФС по сравнению с пациентами без АФС и контрольной группой. Тромбоз ассоциировался с позитивностью IgG-анти-ФС/ПТ. Артериальные тромбозы значимо чаще регистрировались у пациентов с IgG-анти-ФС/ПТ. Чувствительность IgG-анти-ФС/ПТ для достоверного АФС при уровнях позитивности более 73,6 Ед/мл составила 59%, специфичность 92%, для IgМ-анти-ФС/ПТ 35 и 91% соответственно.

Background and aims Immersion during slot machine gambling has been linked to disordered gambling. Current conceptualizations of immersion (namely dissociation, flow and the machine zone) make contrasting predictions as to whether gamblers are captivated by the game per se ('zoned in') or motivated by the escape that immersion provides ('zoned out'). We examined whether selected eye-movement metrics can distinguish between these predictions. Design and setting Pre-registered, correlational analysis in a laboratory setting. Participants gambled on a genuine slot machine for 20 minutes while wearing eye-tracking glasses. Participants Fifty-three adult slot machine gamblers who were not high-risk problem gamblers. Measurements We examined self-reported immersion during the gambling session and eye movements at different areas of the slot machine screen (the reels, the credit window, etc.). We further explored these variables' relationships with saccade count and amplitude. Findings The ratio of dwell time on the game's credit window relative to the game's reels was positively associated with immersion (t(51) = 1.68, P = 0.049 one-tailed, R2 = 0.05). Follow-up analyses described event-related changes in these patterns following different spin outcomes. Conclusions Immersion while gambling on a slot machine appears to be associated with active scanning of the game and a focus on the game's credit window. These results are more consistent with a 'zoned in' account of immersion aligned with flow theory than a 'zoned out' account based on escape.

Modern slot machines are among the more harmful forms of gambling. Psychophysiological measures may provide a window into mental processes that underpin these harms. Here we investigated pupil dilation derived from eye tracking as a means of capturing changes in sympathetic nervous system arousal following outcomes on a real slot machine. We hypothesized that positively reinforcing slot machine outcomes would be associated with increases in arousal, reflected in larger pupil diameter. We further examined the contribution of game luminance fluctuations on pupil diameter. In Experiment 1A, experienced slot machine gamblers (N = 53) played a commercially-available slot machine in a laboratory for 20 minutes while wearing mobile eye tracking glasses. Analyses differentiated loss outcomes, wins, losses-disguised-as-wins, and (free-spin) bonus features. Bonus features were associated with rapid increases in pupil diameter following the onset of outcome-related audiovisual feedback, relative to losses. In Experiment 1B, luminance data were extracted from captured screen videos (derived from Experiment 1A) to characterize on-screen luminance changes that could modulate pupil diameter. Bonus features and wins were associated with pronounced and complex fluctuations in screen luminance (≈50 L and ≈25L, respectively). However, the pupil dilation that was observed to bonus features in Experiment 1A coincided temporally with only negligible changes in screen luminance, providing partial evidence that the pupil dilation to bonus features may be due to arousal. In Experiment 2, 12 participants viewed pairs of stimuli (scrambled slot machine images) at luminance difference thresholds of ≈25L, ≈50L, and ≈100L. Scrambled images presented at luminance differences of ≈25L and greater were sufficient to cause pupillary responses. Overall, pupillometry may detect event-related changes in sympathetic nervous system arousal following gambling outcomes, but researchers must pay careful attention to substantial in-game luminance changes that may confound arousal-based interpretations.

Introduction Clinical evidence suggests that Parkinson's Disease (PD) patients are risk averse. Dopaminergic therapy has been reported to increase risk tolerance, but the underlying mechanisms are unclear. Some studies have suggested an amplification of subjective reward value, consistent with the role of dopamine in reward value coding. Others have reported value-independent risk enhancement. We evaluated the value-dependence of the effects of PD and its therapy on risk using tasks designed to sensitively measure risk over a wide range of expected values. Method 36 patients with idiopathic PD receiving levodopa monotherapy and 36 healthy matched controls performed two behavioural economic tasks aimed at quantifying 1) risk tolerance/aversion in the gain frame and 2) valuation of potential gains relative to losses. PD patients performed the tasks on and off their usual dose of levodopa in randomized order; controls performed the same tasks twice. Results Relative to the controls, unmedicated PD patients showed significant value-independent risk aversion in the gain frame, which was normalized by levodopa. PD patients did not differ from controls in their valuation of gains relative to losses. However, across both tasks and regardless of medication, choices of the patients were more determined by expected values of the prospects than those of controls. Conclusion Dopamine deficiency in PD was associated with risk aversion, and levodopa promoted riskier choice in a value-independent manner. PD patients also showed an increased sensitivity to expected value, which was independent of levodopa and does not appear to result directly from dopamine deficiency.

Background and aimsIndividuals with gambling disorder display increased levels of risk-taking, but it is not known if it is associated with an altered subjective valuation of gains and/or losses, perception of their probabilities, or integration of these sources of information into expected value.MethodsParticipants with gambling disorder (n = 48) were compared with a healthy comparison group (n = 35) on a two-choice lottery task that involved either gains-only or losses-only gambles. On each trial, two lotteries were displayed, showing the associated probability and magnitude of the possible outcome for each. On each trial, participants chose one of the two lotteries, and the outcome was revealed.ResultsChoice behaviour was highly sensitive to the expected value of the two gambles in both the gain and loss domains. This sensitivity to expected value was attenuated in the group with gambling disorder. The group with gambling disorder used both probability and magnitude information less, and this impairment was greater for probability information. By contrast, they used prior feedback (win vs loss) to inform their next choice, despite the independence of each trial. Within the gambling disorder group, problem gambling severity and trait gambling-related cognitions independently predicted reduced sensitivity to expected value. The majority of observed effects were consistent across both gain and loss domains.Discussion and ConclusionsOur results provide a thorough characterization of decision processes in gain and loss domains in gambling disorder, and place these problems in the context of theoretical constructs from behavioural economics.

Current methods using a single PET scan to detect voxel-level transient dopamine release—using F-test (significance) and cluster size thresholding—have limited detection sensitivity for clusters of release small in size and/or having low release levels. Specifically, simulations show that voxels with release near the peripheries of such clusters are often rejected—becoming false negatives and ultimately distorting the F-distribution of rejected voxels. We suggest a Monte Carlo method that incorporates these two observations into a cost function, allowing erroneously rejected voxels to be accepted under specified criteria. In simulations, the proposed method improves detection sensitivity by up to 50% while preserving the cluster size threshold, or up to 180% when optimizing for sensitivity. A further parametric-based voxelwise thresholding is then suggested to better estimate the release dynamics in detected clusters. We apply the Monte Carlo method to a pilot scan from a human gambling study, where additional parametrically unique clusters are detected as compared to the current best methods—results consistent with our simulations.

Reward-related stimuli can potently influence behavior; for example, exposure to drug-paired cues can trigger drug use and relapse in people with addictions. Psychological mechanisms that generate such outcomes likely include cue-induced cravings and attentional biases. Recent animal data suggest another candidate mechanism: reward-paired cues can enhance risky decision making, yet whether this translates to humans is unknown. Here, we examined whether sensory reward-paired cues alter decision making under uncertainty and risk, as measured respectively by the Iowa Gambling Task and a two-choice lottery task. In the cued versions of both tasks, gain feedback was augmented with reward-concurrent audiovisual stimuli. Healthy human volunteers (53 males, 78 females) performed each task once, one with and the other without cues (cued Iowa Gambling Task/uncued Vancouver Gambling Task:n= 63; uncued Iowa Gambling Task/cued Vancouver Gambling Task:n= 68), with concurrent eye-tracking. Reward-paired cues did not affect choice on the Iowa Gambling Task. On the two-choice lottery task, the cued group displayed riskier choice and reduced sensitivity to probability information. The cued condition was associated with reduced eye fixations on probability information shown on the screen and greater pupil dilation related to decision and reward anticipation. This pupil effect was unrelated to the risk-promoting effects of cues: the degree of pupil dilation for risky versus risk-averse choices did not differ as a function of cues. Together, our data show that sensory reward cues can promote riskier decisions and have additional and distinct effects on arousal.SIGNIFICANCE STATEMENTAnimal data suggest that reward-paired cues can promote maladaptive reward-seeking by biasing cost-benefit decision making. Whether this finding translates to humans is unknown. We examined the effects of salient reward-paired audiovisual cues on decision making under risk and uncertainty in human volunteers. Cues had risk-promoting effects on a risky choice task and independently increased task-related arousal as measured by pupil dilation. By demonstrating risk-promoting effects of cues in human participants, our data identify a mechanism whereby cue reactivity could translate into maladaptive behavioral outcomes in people with addictions.

The benefits of exercise in PD have been linked to enhanced dopamine (DA) transmission in the striatum.To examine differences in DA release, reward signaling, and clinical features between habitual exercisers and sedentary subjects with PD.Eight habitual exercisers and 9 sedentary subjects completed [[Habitual exercise is associated with preservation of motor and nonmotor function, possibly mediated by increased DA release. This study formulates a foundation for prospective, randomized controlled studies. © 2018 International Parkinson and Movement Disorder Society.

Summary Background Markers of neuroinflammation are increased in some patients with LRRK2 Parkinson's disease compared with individuals with idiopathic Parkinson's disease, suggesting possible differences in disease pathogenesis. Previous PET studies have suggested amplified dopamine turnover and preserved serotonergic innervation in LRRK2 mutation carriers. We postulated that patients with LRRK2 mutations might show abnormalities of central cholinergic activity, even before the diagnosis of Parkinson's disease. Methods Between June, 2009, and December, 2015, we recruited participants from four movement disorder clinics in Canada, Norway, and the USA. Patients with Parkinson's disease were diagnosed by movement disorder neurologists on the basis of the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. We used the PET tracer N-11C-methyl-piperidin-4-yl propionate to scan for acetylcholinesterase activity. The primary outcome measure was rate of acetylcholinesterase hydrolysis, calculated using the striatal input method. We compared acetylcholinesterase hydrolysis rates between groups using ANCOVA, with adjustment for age based on the results of linear regression analysis. Findings We recruited 14 patients with LRRK2 Parkinson's disease, 16 LRRK2 mutation carriers without Parkinson's disease, eight patients with idiopathic Parkinson's disease, and 11 healthy controls. We noted significant between-group differences in rates of acetylcholinesterase hydrolysis in cortical regions (average cortex p=0·009, default mode network-related regions p=0·006, limbic network-related regions p=0·020) and the thalamus (p=0·008). LRRK2 mutation carriers without Parkinson's disease had increased acetylcholinesterase hydrolysis rates compared with healthy controls in the cortex (average cortex, p=0·046). Patients with LRRK2 Parkinson's disease had significantly higher acetylcholinesterase activity in some cortical regions (average cortex p=0·043, default mode network-related regions p=0·021) and the thalamus (thalamus p=0·004) compared with individuals with idiopathic disease. Acetylcholinesterase hydrolysis rates in healthy controls were correlated inversely with age. Interpretation LRRK2 mutations are associated with significantly increased cholinergic activity in the brain in mutation carriers without Parkinson's disease compared with healthy controls and in LRRK2 mutation carriers with Parkinson's disease compared with individuals with idiopathic disease. Changes in cholinergic activity might represent early and sustained attempts to compensate for LRRK2-related dysfunction, or alteration of acetylcholinesterase in non-neuronal cells. Funding Michael J Fox Foundation, National Institutes of Health, and Pacific Alzheimer Research Foundation.

Objective: Recent trials have demonstrated efficacy of cognitive behavioral therapy (CBT) in medicated adults with ADHD. Efficacy of CBT in unmedicated versus medicated adults remains mostly unknown. We evaluated the effects of group CBT alone versus combined with medication on ADHD symptoms and functional outcomes in adult patients. Method: Eighty-eight adults with ADHD received 12 manualized group CBT sessions, accompanied by individual coaching, either without ( n = 46) or with ( n = 42) medication. Treatment effects were evaluated following treatment and 3-month and 6-month follow-up using un-blinded self-report and observer ratings. Results: CBT + medication resulted in greater improvements than CBT alone in ADHD symptoms, organizational skills, and self-esteem. Group differences diminished over follow-up, as the CBT alone group continued improving, while the combined group maintained the gains. Conclusion: CBT + medication outperformed CBT alone for ADHD symptoms, organizational skills, and self-esteem, although its superiority tended to decrease over follow-up.

Patient responses to placebo and sham effects are a major obstacle to the development of therapies for brain disorders, including Parkinson’s disease (PD). Here, we used functional brain imaging and network analysis to study the circuitry underlying placebo effects in PD subjects randomized to sham surgery as part of a double-blind gene therapy trial. Metabolic imaging was performed prior to randomization, then again at 6 and 12 months after sham surgery. In this cohort, the sham response was associated with the expression of a distinct cerebello-limbic circuit. The expression of this network increased consistently in patients blinded to treatment and correlated with independent clinical ratings. Once patients were unblinded, network expression declined toward baseline levels. Analogous network alterations were not seen with open-label levodopa treatment or during disease progression. Furthermore, sham outcomes in blinded patients correlated with baseline network expression, suggesting the potential use of this quantitative measure to identify “sham-susceptible” subjects before randomization. Indeed, Monte Carlo simulations revealed that a priori exclusion of such individuals substantially lowers the number of randomized participants needed to demonstrate treatment efficacy. Individualized subject selection based on a predetermined network criterion may therefore limit the need for sham interventions in future clinical trials.

Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [(11)C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87 ± 8.65) and 18 healthy male controls (age: 25.44 ± 6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [(11)C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [(11)C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.

The meso-striatal dopamine system influences responses to rewards and the motivation to seek them out. Marked individual differences in these responses are seen in laboratory animals, related in part to input from the prefrontal cortex. Here we measured the relation between cortical morphology and drug-induced striatal dopamine release in healthy young people. Participants were 24 (17 male, 7 female; age 23.0 ± 6.2 years) stimulant drug-naive subjects who underwent PET [11C]raclopride scans with 0.3 mg/kg d-amphetamine orally and placebo, and an anatomical MRI scan for measuring cortical thickness. As expected, d-amphetamine produced significant reductions in [11C]raclopride binding potential in the striatum as a percentage of the value in the placebo condition. There was substantial individual variability in this response, which was correlated with cortical thickness in the frontal lobe as a whole. The association was strongest in the anterior part of the right lateral prefrontal cortex and bilateral supplementary motor area. A thicker cortex was correlated with a smaller dopamine response. Together, this work demonstrates in humans an association between cortical thickness and the striatal dopamine response to drugs of abuse. Although prefrontal regulation of striatal function has been well studied, it was unclear whether the thickness of the prefrontal cortex was an acceptable proxy to the function of that region. These results suggest it is.

Background: Patients with social developmental disorders (SDD), also known as autism spectrum disorders, may have impaired recognition of facial identity or facial expressions. Objective: Our goal was to determine whether SDDs were characterized by loss of a perceptual mechanism responsible for face expertise, as current theories suggest that such a loss should be selective for upright faces, disproportionately affect the perception of facial configuration, and possibly be more severe in the eye region. Method: We tested a group of 24 adult patients with SDD with an oddity paradigm that required them to detect changes in facial configuration or feature color, in either the eyes or the mouth, in both upright and inverted faces. Results: One group of subjects with SDD with normal famous face recognition had only a mild reduction in accuracy and a normal pattern of inversion effects. A second group of subjects with SDD with impaired famous face recognition had a severe reduction of accuracy. This deficit was not limited to upright faces. It affected the perception of feature configuration and feature color to a similar degree and both eye and mouth changes were discriminated poorly in upright faces. Conclusion: The impaired face recognition that is present in a subset of patients with social developmental disorders is accompanied by impaired face perception, and this impairment is not exclusive to upright faces, facial configuration, or the eye region. The reduced face processing skills in these subjects may be more consistent with recent computational models of face expertise than with classic dual-route hypotheses.

The scan patterns of ocular fixations made by prosopagnosic patients while they attempt to identify faces may provide insights into how they process the information in faces. Contrasts between their scanning of upright versus inverted faces may index the presence of a hypothesized orientation-dependent expert mechanism for processing faces, while contrasts between their scanning of familiar versus novel faces may index the influence of residual facial memories on their search for meaningful facial information. We recorded the eye movements of two prosopagnosics while they viewed faces. One patient, with acquired prosopagnosia from a right occipitotemporal lesion, showed degraded orientation effects but still with a normal distribution of fixations to more salient facial features. However, the dynamics of his global scan patterns were more chaotic for novel faces, suggesting degradation of an internal facial schema, and consistent with other evidence of impaired face configuration perception in this patient. His global scan patterns for famous faces differed from novel faces, suggesting the influence of residual facial memories, as indexed previously by his relatively good imagery for famous faces. The other patient, with a developmental prosopagnosia, showed anomalous orientation effects, abnormal distribution of fixations to less salient regions, and chaotic global scan patterns, in keeping with a more severe loss of face-expert mechanisms. The effects of fame on her scanning were weaker than those in the first subject and non-existent in her global scan patterns. We conclude that scan patterns in prosopagnosia can both reflect the loss of orientation-dependent expert mechanisms and index the covert influence of residual facial memories. In these two subjects the scanning data were consistent with other results from tests of configuration perception, imagery, and covert recognition.

Where we make ocular fixations when viewing an object likely reflects interactions between ‘external’ object properties and internal ‘top - down’ factors, as our perceptual system tests hypotheses and attempts to make decisions about our environment. These scanning fixation patterns can tell us how and where the visual system gathers information critical to specific tasks. We determined the effects of the internal factors of expertise, experience, and ambiguity on scanning during a face-recognition task, in eight subjects. To assess the effects of expertise, we compared upright with inverted faces, since it is hypothesized that inverted faces do not access an orientation-dependent face-expert processor. To assess the effects of experience, we compared famous with novel faces, as famous faces would have stronger internal representations than anonymous ones. Ambiguity in matching seen and remembered faces was manipulated with morphed faces. We measured three classes of variables: (i) total scanning time and fixations; (ii) the spatial distribution of scanning; and (iii) the sequence of scanning, using first-order Markov matrices for local scan structure and string editing for global scan structure. We found that, with inverted faces, subjects redistributed fixations to the mouth and lower face, and their local and global scan structure became more random. With novel or morphed faces, they scanned the eyes and upper face more. Local scan structure was not affected by familiarity, but global scan structure was least random (most stereotyped) for novel upright faces. We conclude that expertise (upright faces) leads to less lower-face scanning and more predictable global patterns of information gathering. Experience (famous faces) leads to less upper-face scanning and more idiosyncratic global scan structures, suggesting a superseding influence of facial memories. With morphed faces, subjects return to the upper face to resolve ambiguity, implying a greater importance of this region in face recognition.

Although perseveration is sometimes attributed to defective set switching, the authors have recently shown that set-switching is normal in schizophrenia. In this article, the authors tested for persistent states of the saccadic response system, rather than set perseveration. Schizophrenic and healthy subjects performed antisaccades and prosaccades. The authors analyzed for 3 carry-over effects. First, whereas the latency of the current saccade correlated with that of the prior saccade in both groups, the correlations under mixed-task conditions declined in healthy but not in schizophrenic subjects. Second, antisaccades in penultimate trials delayed upcoming saccades in schizophrenic but not in healthy subjects. Third, schizophrenic subjects were more likely to erroneously perseverate the direction of a prior antisaccade but not a prior prosaccade. The authors concluded that, in schizophrenia, the effects of correct antisaccades are persistent not weak. Saccades in schizophrenia are characterized by perseveration of antisaccade-induced changes in the saccadic response system rather than failures to switch task set.

Background: There are many methods of testing covert face recognition in prosopagnosia, but it is not clear whether different types of covert recognition share a common mechanism. Objective: To determine whether direct forced-choice techniques and indirect face-priming methods yielded similar behavioral estimates of covert ability in a series of prosopagnosic patients. Methods: The authors tested seven control subjects and seven prosopagnosic patients. Six patients had an apperceptive prosopagnosia: one with childhood onset, three with bilateral lesions, and two with unilateral occipitotemporal lesions. The last had an associative prosopagnosia from bilateral anterior temporal lesions. The direct tests of covert function involved sorting faces by occupation or the forced choosing of which of two faces was famous with a name cue. The indirect test assessed name classification by occupation after priming with a facial stimulus. Results: In normal subjects, the chief priming effect was facilitation by the true face. In the six patients with apperceptive prosopagnosia, direct covert measures were correlated with the face-priming effect, with better covert ability in patients with unilateral posterior lesions. In the patient with associative prosopagnosia, there was a dissociation between excellent direct covert function and absent face priming. Conclusions: Direct and indirect covert functions likely share similar mechanisms in patients with apperceptive prosopagnosia and may reflect residual activity in anterior and left hemispheric components of the normal face-processing network. However, face priming may be ineffectual in patients with severely degraded facial memories from anterior temporal damage. This may indicate a difference between residual patterns of face-related activity in associative and apperceptive prosopagnosia.

Some patients with prosopagnosia may have an apperceptive basis to their recognition defect. Perceptual abnormalities have been reported in single cases or small series, but the causal link of such deficits to prosopagnosia is unclear. Our goal was to identify candidate perceptual processes that might contribute to prosopagnosia, by subjecting several prosopagnosic patients to a battery of functions that may be necessary for accurate facial perception. We tested seven prosopagnosic patients. Three had unilateral right occipitotemporal lesions, two had bilateral posterior occipitotemporal lesions, and one had right anterior-to-occipital temporal damage along with a small left temporal lesion. These lesions all included the fusiform face area, in contrast to one patient with bilateral anterior temporal lesions. Most patients had impaired performance on face-matching tests and difficulty with subcategory judgments for non-face objects. The most consistent deficits in patients with lesions involving the fusiform face area were impaired perception of spatial relations in dot patterns and reduced contrast sensitivity in the 4 to 8 cycles deg−1 range. Patients with bilateral lesions were impaired in saturation discrimination. Luminance discrimination was normal in all but two patients, and spatial resolution was uniformly spared. Curvature and line-orientation discrimination were impaired in only one patient, who also had the most difficulty with more basic-level object recognition. We conclude that deficits in luminance, spatial resolution, curvature, line orientation, and contrast at low spatial frequencies are unlikely to contribute to apperceptive prosopagnosia. More relevant may be contrast sensitivity at higher spatial frequencies and the analysis of object spatial structure. Deficits in these functions may impair perception of subtle variations in object shape, and may be one mechanism by which the recognition defect in prosopagnosia can extend to other classes of object subcategorization.

Summary It has been hypothesized that social developmental disorders (SDD) like autism, Asperger’s disorder and the social-emotional processing disorder may be associated with prosopagnosic-like deficits in face recognition. We studied the ability to recognize famous faces in 24 adults with a variety of SDD diagnoses. We also measured their ability to discriminate changes in internal facial configuration, a perceptual function that is important in face recognition, and their imagery for famous faces, an index of their facial memory stores. We contrasted their performance with both healthy subjects and prosopagnosic patients. We also performed a cluster analysis of the SDD patients. One group of eight SDD subjects performed normally on all tests of face perception and recognition. The other 16 subjects were impaired in recognition, though most were better than prosopagnosic patients. One impaired SDD subgroup had poor perception of facial structure but relatively preserved imagery, resembling prosopagnosic patients with medial occipitotemporal lesions. Another subgroup had better perception than imagery, resembling one prosopagnosic with bilateral anterior temporal lesions. Overall, SDD subgroup membership by face recognition did not correlate with a particular SDD diagnosis or subjective ratings of social impairment.We conclude that the social disturbance in SDD does not invariably lead to impaired face recognition. Abnormal face recognition in some SDD subjects is related to impaired perception of facial structure in a manner suggestive of occipitotemporal dysfunction. Heterogeneity in the perceptual processing of faces may imply pathogenetic heterogeneity, with important implications for genetic and rehabilitative studies of SDD.

Background Novelty-seeking (NS) and impulsive personality traits have been proposed to reflect an interplay between fronto-cortical and limbic systems, including the limbic striatum (LS). Although neuroimaging studies have provided some evidence for this, most are comprised of small samples and many report surprisingly large effects given the challenges of trying to relate a snapshot of brain function or structure to an entity as complex as personality. The current work tested a priori hypotheses about associations between striatal dopamine (DA) release, cortical thickness (CT), and NS in a large sample of healthy adults. Methods Fifty-two healthy adults (45M/7F; age: 23.8±4.93) underwent two positron emission tomography scans with [11C]raclopride (specific for striatal DA D2/3 receptors) with or without amphetamine (0.3 mg/kg, p.o.). Structural magnetic resonance image scans were acquired, as were Tridimensional Personality Questionnaire data. Amphetamine-induced changes in [11C]raclopride binding potential values (ΔBPND) were examined in the limbic, sensorimotor (SMS) and associative (AST) striatum. CT measures, adjusted for whole brain volume, were extracted from the dorsolateral sensorimotor and ventromedial/limbic cortices. Results BPND values were lower in the amphetamine vs. no-drug sessions, with the largest effect in the LS. When comparing low vs. high LS ΔBPND groups (median split), higher NS2 (impulsiveness) scores were found in the high ΔBPND group. Partial correlations (age and gender as covariates) yielded a negative relation between ASTS ΔBPND and sensorimotor CT; trends for inverse associations existed between ΔBPND values in other striatal regions and frontal CT. In other words, the greater the amphetamine-induced striatal DA response, the thinner the frontal cortex. Conclusions These data expand upon previously reported associations between striatal DA release in the LS and both NS related impulsiveness and CT in the largest sample reported to date. The findings add to the plausibility of these associations while suggesting that the effects are likely weaker than has been previously proposed.

Mental training techniques rooted in meditation are associated with attention improvement, increased activation and cortical thickening of attention/executive-related brain areas. Interestingly, attention-deficit/hyperactivity disorder (ADHD) is associated with behavioural deficits, hypo-activation and cortical thinning of similar networks. This study assessed the relationship between prior meditative training, attentional absorption, and cortical thickness. Grey matter thickness was measured in 18 meditators and 18 controls. Subjective reports of attentional absorption were modestly higher in meditators and across the entire sample correlated positively with cortical thickness in several regions corresponding to cingulo-fronto-parietal attention networks. Within these regions the meditation group had greater cortical thickness which was positively related to the extent of prior training. Evidence suggesting that meditative practice activates these cortical areas, improves attention and may ameliorate symptoms of ADHD by targeting vulnerable brain regions is discussed.

Objectives:To review the findings of structural and functional neuroimaging studies in attention-deficit hyperactivity disorder (ADHD), with a focus on abnormalities reported in brain regions that lie outside the frontostriatal circuitry, which is currently believed to play a central role in the pathophysiology of ADHD.Methods:Relevant publications were found primarily by searching the MEDLINE and PubMed databases using the keywords ADHD and the abbreviations of magnetic resonance imaging (MRI), functional MRI, positron emission tomography, and single photon emission computed tomography. The reference lists of the articles found through the databases were then reviewed for the purpose of finding additional articles.Results:There is now substantial evidence of structural and functional alterations in regions outside the frontostriatal circuitry in ADHD, most notably in the cerebellum and the parietal lobes.Conclusions:Although there is compelling evidence suggesting that frontostriatal dysfunction may be central to the pathophysiology of ADHD, the neuroimaging findings point to distributed neural substrates rather than a single one. More research is needed to elucidate the nature of contributions of nonfrontostriatal regions to the pathophysiology of ADHD.

Background: Patients with prosopagnosia from occipitotemporal lesions have impaired perception of the configuration of facial features. This may be an example of impaired “within-object” spatial coding, which others propose to be distinct from “between-object” spatial coding. Objective: To determine whether the prosopagnosic deficit in perceiving spatial configuration was specific to within-face and not between-face spatial coding and whether the deficit was face-selective or extended to objects other than faces. Methods: Six prosopagnosic patients were tested using an oddity paradigm in which they detected which of three simultaneously seen stimuli was an altered target. In the “within-face” task, the target face had altered interocular distance or mouth position. In the “between-face” task, the target face was located farther away from the other two. In the “within-object” task, the stimulus was a two-dot pattern, and the target pattern had altered interdot distance. Results: Spatial judgments were impaired within faces for all six patients and within the two-dot pattern for five of six patients. However, all six had normal between-face spatial perception. Conclusions: Impaired perception of spatial relations in prosopagnosia is selective to the spatial structure within individual objects and spares the perception of spatial location of objects. It is not specific to faces. It reveals a process involved in analyzing object structure, consistent with the patients’ deficits in recognizing facial identity, and illustrates a different type of “visuospatial” defect.

Background: Face imagery can access facial memories without the use of perceptual stimuli. Current data on the relation of imagery to the perceptual function and neuroanatomy of prosopagnosic patients are mixed, and little is known about the type of facial information patients can access through imagery. Objective: The authors wished to determine 1) which lesions abolished face imagery in prosopagnosia, 2) if deficits in perceiving facial structure were paralleled by similar deficits in imagery, and 3) if covert recognition of faces correlated with the degree of residual imagery for faces. Methods: The authors tested nine prosopagnosic patients who had been tested previously for perception of facial configuration and covert recognition of famous faces. The authors constructed a battery of 37 questions that asked subjects to imagine the faces of two celebrities and to choose which one had a certain facial property. Half were questions about facial features and half were about overall facial shape. Results: Imagery was abolished only by anterior temporal lesions. Imagery for facial shape but not features was degraded by lesions of the right hemisphere’s fusiform face area, which severely impaired perception of facial configuration. Feature imagery was degraded only when there was associated left occipito-temporal damage. Covert recognition was found when either configural perception or imagery was severely damaged, but not when both were abnormal. In patients with impaired configural perception, covert recognition correlated with feature imagery, suggesting that feature-based processing may drive residual covert abilities in these patients. Conclusion: Although anterior temporal cortex may be the site of facial memory stores, these data also support hypotheses that perceptual areas like the fusiform face area have parallel contributions to mental imagery. The data on covert recognition are consistent with a view that it is the residue of a partially damaged face-recognition network. Covert recognition may reflect the degree of damage across components of a network rather than mark a specific form of prosopagnosia or a dissociated pathway.

We studied perception in three patients with prosopagnosia of childhood onset. All had trouble with other ‘within-category’ judgments. All were deficient on face matching tests and severely impaired on tests of perception of the spatial relations of facial features and abstract designs, indicating a deficit in the encoding of coordinate relationships, similar to adult-onset prosopagnosia with lesions of the fusiform face area. Two had difficulty perceiving feature colour, which correlated with reduced luminance sensitivity. In contrast to adult-onset patients, saturation discrimination was spared in two and spatial resolution impaired in two. Curvature discrimination was relatively spared. Contrast sensitivity showed variable reductions at different spatial frequencies. We conclude that developmental prosopagnosia is similar to the adult-onset form in encoding deficits for the spatial arrangement of facial elements. Deficits in luminance perception and spatial resolution are more associated with defective encoding for basic object-level recognition, as shown on tests of object and spatial perception.

Background: Schizophrenic patients have executive function deficits, presumably on the basis of prefrontal cortex dysfunction. Although they consistently show impaired inhibition, the evidence of a task switching deficit is less consistent and is often based on performance of neuropsychological tests that require several cognitive processes (e.g., the Wisconsin Card Sort Test [WCST]). We investigated inhibition and task switching using saccadic tasks to determine whether schizophrenic patients have selective impairments of these executive functions. Methods: Sixteen normal and 21 schizophrenic subjects performed blocks of randomly mixed prosaccade and antisaccade trials. This gave rise to four trial types: prosaccades and antisaccades that were either repeated or switched. Response accuracy and latency were measured. Schizophrenic subjects also performed the WCST. Results: Schizophrenic subjects showed abnormal antisaccade and WCST performance. In contrast, task switching was normal and unrelated to either antisaccade or WCST performance. Conclusions: The finding of intact task switching performance that is unrelated to other measures of executive function demonstrates selective rather than general impairments of executive functions in schizophrenia. The findings also suggest that abnormal WCST performance is unlikely to be a consequence of deficient task switching. We hypothesize that inhibition and task switching are mediated by distinct neural networks, only one of which is dysfunctional in schizophrenia.

Executive functions allow us to respond flexibly rather than stereotypically to the environment. We examined two such functions, task switching and inhibition in the antisaccade paradigm, in two studies. One study involved 18 normal subjects; the other, 21 schizophrenic patients and 16 age-matched controls. Subjects performed blocks of randomly mixed prosaccades and antisaccades. Repeated trials were preceded by the same type of trial (i.e., an antisaccade following an antisaccade), and switched trials were preceded by a trial of the opposite type. We measured accuracy rate and latency as indices of processing costs. Whereas schizophrenic patients had a threefold increase in error rate for antisaccades compared to normals, the effect of task switching on their accuracy did not differ from that in normal subjects. Moreover, the accuracy rate of trials combining antisaccade and task switching was equivalent to a multiplication of the accuracy rates from trials in which each was done alone. Schizophrenic latencies were disproportionately increased for antisaccades, but again they were no different from normal subjects in the effect of task switching. In both groups the effect of task switching on antisaccades was a paradoxical latency reduction. We conclude that the executive dysfunction in schizophrenia is not generalized but selective, sparing task switching from exogenous cues, in which the switch is limited to a stimulus-response remapping. The accuracy data in both groups support independence of antisaccade and task-switching functions. The paradoxical task-switching benefit in antisaccadic latency effects challenges current models of task switching. It suggests either carryover inhibition by antisaccadic performance in the prior trial or facilitation of antisaccades by simultaneous performance of other cognitive operations.

Smaller latency costs for switching from dominant (habitual) to non-dominant (unusual) tasks compared to the reverse direction have been noted in some studies of task-switching. This asymmetry has been cited as evidence of inhibitory effects from the prior trial. We examined accuracy and latency costs of task-switching between prosaccades and antisaccades, where task-switching is limited to stimulus-response re-mapping and occurs between tasks highly asymmetric in dominance. Eighteen subjects executed prosaccades and antisaccades in single-task and mixed-task blocks. In mixed-task blocks, antisaccade and prosaccade trials were ordered randomly, resulting in 'repeated' trials that were preceded by the same type of trial (i.e. antisaccade-antisaccade), and 'switched' trials that were preceded by the opposite type of trial. Comparisons of the single-task blocks and repeated trials of the mixed-task blocks indexed the mixed-list costs, which were small for prosaccades and insignificant for antisaccades. Comparison of the repeated and switched trials from the mixed-task blocks indexed the residual task-switch cost. Accuracy costs of task-switching and antisaccades were equivalent. The accuracy of trials incorporating both switching and antisaccades in a single response (i.e. switched antisaccade) equalled the product of the accuracies of doing each operation alone, supporting independence of these two functions. In contrast, the latency cost of antisaccade performance was 3 times greater than that of task-switching. Task-switching from prosaccades to antisaccades resulted in a paradoxical decrease in antisaccade latency. This decrease correlated with other indices of vigilance, with the paradoxical effect minimized in more attentive observers. The latency data suggest that either an antisaccade on the prior trial perturbs saccadic responses more than a task-switch, or concurrent task-switching specifically facilitates antisaccades. In either case, the paradoxical benefit of task-switching for antisaccades challenges current models of task-switching.