The sensory input that we experience is highly patterned, and we are experts at detecting these regularities. Although the extraction of such regularities, or statistical learning (SL), is typically viewed as a cortical process, recent studies have implicated the medial temporal lobe (MTL), including the hippocampus. These studies have employed fMRI, leaving open the possibility that the MTL is involved but not necessary for SL. Here, we examined this issue in a case study of LSJ, a patient with complete bilateral hippocampal loss and broader MTL damage. In Experiments 1 and 2, LSJ and matched control participants were passively exposed to a continuous sequence of shapes, syllables, scenes, or tones containing temporal regularities in the co-occurrence of items. In a subsequent test phase, the control groups exhibited reliable SL in all conditions, successfully discriminating regularities from recombinations of the same items into novel foil sequences. LSJ, however, exhibited no SL, failing to discriminate regularities from foils. Experiment 3 ruled out more general explanations for this failure, such as inattention during exposure or difficulty following test instructions, by showing that LSJ could discriminate which individual items had been exposed. These findings provide converging support for the importance of the MTL in extracting temporal regularities.
A rich literature suggests that both impulsiveness and drug-induced euphoria are risk factors for drug abuse. However, few studies have examined whether sensitivity to the euphoric effects of stimulants is related to attention lapses, a behavioral measure of inattention sometimes associated with impulsivity.
The aim of the study was to examine ratings of d-amphetamine drug liking among individuals with high, moderate, and low attention lapses.
Ninety-nine healthy volunteers were divided into three equal-sized groups based on their performance on a measure of lapses of attention. The groups, who exhibited low, medium, and high attention lapses (i.e., long reaction times) on a simple reaction time task, were compared on their subjective responses (i.e., ratings of liking and wanting more drug) after acute doses of d-amphetamine (0, 5, 10, and 20 mg).
Subjects who exhibited high lapses liked 20 mg d-amphetamine less than subjects who exhibited low lapses. These subjects also tended to report smaller increases in “wanting more drug” after d-amphetamine.
The findings suggest that participants who exhibit impaired attention may be less sensitive to stimulant-induced euphoria.
Inattention d-amphetamine; Reward; Drug liking; Subjective effects; Dopamine; Impulsiveness
Alcohol has been shown to affect performance on tasks associated with executive functioning. However, studies in this area have generally been limited to a single dose or gender or have used small sample sizes. The purpose of this study was to provide a more nuanced and systematic examination of alcohol's effects on commonly used tests of executive functioning at multiple dosages in both men and women. Research volunteers (91 women and 94 men) were randomly assigned to one of four drink conditions (alcohol doses associated with target blood alcohol concentrations of .000%, .050%, .075% and .100%). Participants then completed three tasks comprising two domains of executive functioning: two set shifting tasks, the Trail Making Test and a computerized version of the Wisconsin Card Sorting Task, and a response inhibition task, the GoStop Impulsivity Paradigm. Impaired performance on set shifting tasks was found at the .100% and .075% dosages, but alcohol intoxication did not impair performance on the GoStop. No gender effects emerged. Thus, alcohol negatively affects set shifting at moderately high levels of intoxication in both men and women, likely due to alcohol's interference with prefrontal cortex function. Although it is well-established that alcohol negatively affects response inhibition as measured by auditory stop-signal tasks, alcohol does not appear to exert a negative effect on response inhibition as measured by the GoStop, a visual stop-signal task.
Although risky decision-making has been posited to contribute to the maladaptive behavior of individuals with psychopathic tendencies, the performance of psychopathic groups on a common task of risky decision-making, the Iowa Gambling Task (IGT; Bechara, Damasio, Damasio, & Anderson, 1994), has been equivocal. Different aspects of psychopathy (personality traits, antisocial deviance) and/or moderating variables may help to explain these inconsistent findings. In a sample of college students (N = 129, age 18 to 27), we examined the relationship between primary and secondary psychopathic features and IGT performance. A measure of impulsivity was included to investigate its potential as a moderator. In a joint model including main effects and interactions between primary psychopathy, secondary psychopathy and impulsivity, only secondary psychopathy was significantly related to risky IGT performance, and this effect was not moderated by the other variables. This finding supports the growing literature suggesting that secondary psychopathy is a better predictor of decision-making problems than the primary psychopathic personality traits of lack of empathy and remorselessness.
primary psychopathy; secondary psychopathy; impulsivity; risk-taking; decision-making; gambling task; noninstitutionalized
Studies of retrograde amnesia have focused on autobiographical memory, with fewer studies examining how non-autobiographical memory is affected. Those that have done so have focused primarily on memory for famous people and public events—relatively limited aspects of memory that are tied to learning during specific times of life and do not deeply tap into the rich and extensive knowledge structures that are developed over a lifetime. To assess whether retrograde amnesia can also cause impairments to other forms of general world knowledge, we explored losses across a broad range of knowledge domains in a newly-identified amnesic. LSJ is a professional artist, amateur musician and history buff with extensive bilateral medial temporal and left anterior temporal damage. We examined LSJ's knowledge across a range of everyday domains (e.g., sports) and domains for which she had premorbid expertise (e.g., famous paintings). Across all domains tested, LSJ showed losses of knowledge at a level of breadth and depth never before documented in retrograde amnesia. These results show that retrograde amnesia can involve broad and deep deficits across a range of general world knowledge domains. Thus, losses that have already been well-documented (famous people and public events) may severely underestimate the nature of human knowledge impairment that can occur in retrograde amnesia.
memory; general world knowledge; brain damage; retrograde amnesia; single case study
Damage to the hippocampus impairs the ability to acquire new declarative memories, but not the ability to learn simple motor tasks. An unresolved question is whether hippocampal damage affects learning for music performance, which requires motor processes, but in a cognitively complex context. We studied learning of novel musical pieces by sight-reading in a newly identified amnesic, LSJ, who was a skilled amateur violist prior to contracting herpes simplex encephalitis. LSJ has suffered virtually complete destruction of the hippocampus bilaterally, as well as extensive damage to other medial temporal lobe structures and the left anterior temporal lobe. Because of LSJ’s rare combination of musical training and near-complete hippocampal destruction, her case provides a unique opportunity to investigate the role of the hippocampus for complex motor learning processes specifically related to music performance. Three novel pieces of viola music were composed and closely matched for factors contributing to a piece’s musical complexity. LSJ practiced playing two of the pieces, one in each of the two sessions during the same day. Relative to a third unpracticed control piece, LSJ showed significant pre- to post-training improvement for the two practiced pieces. Learning effects were observed both with detailed analyses of correctly played notes, and with subjective whole-piece performance evaluations by string instrument players. The learning effects were evident immediately after practice and 14 days later. The observed learning stands in sharp contrast to LSJ’s complete lack of awareness that the same pieces were being presented repeatedly, and to the profound impairments she exhibits in other learning tasks. Although learning in simple motor tasks has been previously observed in amnesic patients, our results demonstrate that non-hippocampal structures can support complex learning of novel musical sequences for music performance.
music performance; learning; memory; hippocampus; brain damage; anterograde amnesia; single-patient study
This study investigates the discrimination accuracy of emotional stimuli in subjects with major depression compared with healthy controls using photographs of facial expressions of varying emotional intensities. The sample included 88 unmedicated male and female subjects, aged 18 –56 years, with major depressive disorder (n = 44) or no psychiatric illness (n = 44), who judged the emotion of 200 facial pictures displaying an expression between 10% (90% neutral) and 80% (nuanced) emotion. Stimuli were presented in 10% increments to generate a range of intensities, each presented for a 500-ms duration. Compared with healthy volunteers, depressed subjects showed very good recognition accuracy for sad faces but impaired recognition accuracy for other emotions (e.g., harsh, surprise, and sad expressions) of subtle emotional intensity. Recognition accuracy improved for both groups as a function of increased intensity on all emotions. Finally, as depressive symptoms increased, recognition accuracy increased for sad faces, but decreased for surprised faces. Moreover, depressed subjects showed an impaired ability to accurately identify subtle facial expressions, indicating that depressive symptoms influence accuracy of emotional recognition.
recognition accuracy; facial expressions; information processing; major depression
Although many cognitive functions require information about the orientations of objects, little is known about representation or processing of object orientation. Mirror-image confusion provides a potential clue. This phenomenon is typically characterized as a tendency to confuse images related by left-right reflection (reflection across an extrinsic vertical axis). However, in most previous studies the stimuli were inadequate for identifying a specific mirror-image (or other) relationship as the cause of the observed confusions. Using stimuli constructed to resolve this problem, Gregory and McCloskey (2010) found that adults’ errors were primarily reflections across an object axis, and not left-right reflections. The present study demonstrates that young children’s orientation errors include both object-axis reflections and left-right reflections. We argue that children and adults represent object orientation in the same coordinate-system format (McCloskey, 2009), with orientation errors resulting from difficulty encoding or retaining one (adults) or two (children) specific components of the posited representations.
Spatial cognition; orientation; mirror images; object representation; development
Psychotic symptoms are associated with aggressive tendencies, but this relationship is both complex and imperfect. In contrast to psychotic disorders, little is known about aggressive behavior and sub-clinical psychotic symptoms (e.g., “psychosis proneness”), which are relatively common in the general population. Threat/control-override (TCO), which is the propensity to overestimate the likelihood that an outside agent will (1) inflict harm (threat) or (2) control one’s behaviors (control-override), has been associated with aggression in both psychiatric and community samples. The purpose of this study was to determine if psychosis proneness is related to aggression, and if one or both aspects of TCO mediate this relationship. We hypothesized that the propensity to overestimate threat would mediate this relationship, but control-override would not. Sixty men and sixty women (mean age = 20.00 years, sd = 3.00) with no history of psychotic disorder completed measures assessing psychosis proneness, threat control/override, aggressive history, aggressive ideation, and aggressive behavior. Three structural equation models were tested: (1) Threat and control-override modeled as separate mediating variables, (2) TCO as a unitary mediating latent construct, and (3) TCO considered as part of a psychosis-proneness latent variable. Results indicated that psychosis proneness is positively related to aggression and that the best model fit was obtained when threat and control-override were modeled as separate variables, with mediation through threat alone. The utility of TCO for explaining the relation between psychosis spectrum symptoms and aggression is discussed.
Aggression; Psychosis-proneness; Threat; Control-override; Mediation
The presence of a comorbid eating disorder (ED) and personality disorder (PD) is associated with greater problems and poorer functioning than having an ED alone or PD alone. This pattern is also found for non-ED axis I disorders and PDs. This study aims to examine if an ED, compared to other non-ED axis I disorders, in a PD sample confers greater risks for: number and type of non-ED axis I and axis II disorders, suicide attempts and non-suicidal self-injury, and poorer psychosocial functioning. Standardized interviews were conducted on 166 females and 166 males with PDs. In females with PDs, EDs, as compared to other axis I disorders, were associated with more non-ED axis I and II disorders (particularly borderline and avoidant PD) and poorer global functioning, but not with suicide attempts or nonsuicidal self-injury. In males with PDs, EDs were associated with more axis II disorders, particularly borderline PD. Given the small group of males with EDs, these results require replication. Males and females with PDs and EDs may have multiple comorbid disorders, particularly borderline PD and for females, avoidant PD that may warrant targeting in treatment.
comorbidity; suicidal behavior; psychosocial functioning; eating disorders
The purpose of this study was to investigate the ability of astrocyte-derived factors to influence neural progenitor cell differentiation. We previously demonstrated that rat adult hippocampal progenitor cells (AHPCs) immunoreactive for the neuronal marker, class III β-tubulin (TUJ1) were significantly increased in the presence of astrocyte-derived soluble factors under non-contact co-culture conditions. Using whole cell patch clamp analysis, we observed that the co-cultured AHPCs displayed two prominent voltage-gated conductances - tetraethyl ammonium (TEA)-sensitive outward currents and fast transient inward currents. The outward and inward current densities of the co-cultured AHPCs were approximately 2.5-fold and 1.7-fold greater, respectively, than those of cells cultured alone. These results suggest that astrocyte-derived soluble factors induce neuronal commitment of AHPCs. To further investigate the activity of a candidate neurogenic factor on AHPC differentiation, we cultured AHPCs in the presence or absence of purified rat recombinant interleukin-6 (IL-6). We also confirmed that the astrocytes used in this study produced IL-6 by ELISA and RT-qPCR. When AHPCs were cultured with IL-6 for 6-7 days, the TUJ1-immunoreactive AHPCs and the average length of TUJ1-immunoreactive neurites were significantly increased, compared to the cells cultured without IL-6. Moreover, IL-6 increased the inward current density to a comparable extent as did co-culture with astrocytes, with no significant differences in the outward current density, apparent resting potential, or cell capacitance. These results suggest that astrocyte-derived IL-6 may facilitate AHPC neuronal differentiation. Our findings have important implications for understanding injury-induced neurogenesis and developing cell-based therapeutic strategies using neural progenitors.
Neural stem cells; Interleukin-6; Neuronal differentiation; Electrophysiology
The graphemic representations that underlie spelling performance must encode not only the identities of the letters in a word, but also the positions of the letters. This study investigates how letter position information is represented. We present evidence from two dysgraphic individuals, CM and LSS, who perseverate letters when spelling: that is, letters from previous spelling responses intrude into subsequent responses. The perseverated letters appear more often than expected by chance in the same position in the previous and subsequent responses. We used these errors to address the question of how letter position is represented in spelling. In a series of analyses we determined how often the perseveration errors produced maintain position as defined by a number of alternative theories of letter position encoding proposed in the literature. The analyses provide strong evidence that the grapheme representations used in spelling encode letter position such that position is represented in a graded manner based on distance from both edges of the word.
letter position coding; dysgraphia; spelling; letter perseveration errors; orthographic processing
Neuropsychological studies implicate disruption of frontal systems in personality disorders. Few studies have examined the performance of Cluster B and Cluster C personality disorder patients on tests of orbitofrontal (OFC) and prefrontal (PFC) cortex function. Patients carrying diagnoses of either Cluster B (n=56) or Cluster C (n=19) personality disorders were compared with healthy control subjects (n=61) on the Iowa Gambling Task and University of Pennsylvania Smell Identification Test. They also completed the Wechsler Abbreviated Scale of Intelligence as a control for general intellectual ability. On the gambling task, Cluster B and Cluster C patients made more disadvantageous decisions during certain portions of the task but overall did not differ from healthy controls. Whereas no appreciable differences in olfactory identification performances were detected between patient and healthy control groups, IQ was higher for controls and was related to Cluster B patients’ lower educational levels. Overall, there was limited evidence for neurocognitive inefficiency for personality disorder groups on tests sensitive to OFC and PFC function. The present study is among the first to report neurocognitive findings for the full range of Cluster B personality disorders and any Cluster C personality disorder.
borderline personality disorder; olfaction; Iowa Gambling Task; prefrontal cortex; orbitofrontal cortex
We tested the theory that central serotonin (5- hydroxytryptamine, or 5-HT) activity regulates aggression by modulating response to provocation. Eighty men and women (40 with and 40 without a history of aggression) were randomly assigned to receive either 40 mg of paroxetine (to acutely augment serotonergic activity) or a placebo, administered using double-blind procedures. Aggression was assessed during a competitive reaction time game with a fictitious opponent. Shocks were selected by the participant and opponent before each trial, with the loser on each trial receiving the shock set by the other player. Provocation was manipulated by having the opponent select increasingly intense shocks for the participant and eventually an ostensibly severe shock toward the end of the trials. Aggression was measured by the number of severe shocks set by the participant for the opponent. As predicted, aggressive responding after provocation was attenuated by augmentation of serotonin in individuals with a pronounced history of aggression.
Borderline personality disorder (BPD) is marked by aggression and impulsive, often self-destructive behavior. Despite the severe risks associated with BPD, relatively little is known about the disorder’s etiology. Identification of genetic correlates (endophenotypes) of BPD would improve the prospects of targeted interventions for more homogeneous subsets of borderline patients characterized by specific genetic vulnerabilities. The current study evaluated behavioral measures of aggression and impulsivity as potential endophenotypes for BPD. Subjects with BPD (N = 127), a non cluster B personality disorder (OPD N = 122), or healthy volunteers (HV N = 112) completed self report and behavioral measures of aggression, motor impulsivity and cognitive impulsivity. Results showed that BPD subjects demonstrated more aggression and motor impulsivity than HV (but not OPD) subjects on behavioral tasks. In contrast, BPD subjects self-reported more impulsivity and aggression than either comparison group. Subsequent analyses showed that among BPD subjects behavioral aggression was associated with self-reported aggression, while behavioral and self-report impulsivity measures were more modestly associated. Overall, the results provide partial support for the use of behavioral measures of aggression and motor impulsivity as endophenotypes for BPD, with stronger support for behavioral aggression measures as an endophenotype for aggression within BPD samples.
Borderline personality disorder; Endophenotype; Aggression; Impulsivity
This study tests the validity of the ‘dietary-depressive’ subtype (typified by greater negative affect) and a ‘dietary’ subtype (typified by dietary restraint only) using a diverse longitudinal community sample.
Girls at ages 10, 12 and 14 completed the Child Eating Attitudes Test, the Child Symptom Inventory-4, and Body Image Measure. Body Mass Index was assessed at each age.
Unlike previous studies, cluster analysis revealed an at-risk ‘dietary-depressive’ (R+) subtype (18.7%,100/534) and a not at-risk (R−) subtype, distinguished by few depressive symptoms and little dietary restraint (81.3%,434/534), but no ‘dietary’ subtype. Compared to the R− subtype, the R+ subtype had significantly greater eating disordered behavior and attitudes. The R+ subtype at age 10 was a risk factor for binge-eating but not obesity at ages 12 and 14.
Dietary restraint and depressive symptoms combined predict binge-eating longitudinally in a diverse community sample of girls.
Functional imaging studies have begun to identify a set of brain regions whose brain activity is greater during ‘rest’ (e.g., fixation) states than during cognitive tasks. It has been posited that these regions constitute a network that supports the brain's default mode, which is temporarily suspended during specific goal-directed behaviors. Exogenous tasks that require cognitive effort are thought to command reallocation of resources away from the brain's default state. However, it remains unknown if brain activity during fixation periods between active task periods is influenced by previous task-related emotional content. We examined brain activity during periods of FIXATION (viewing and rating gray-scale images) interspersed among periods of viewing and rating complex images (‘PICTURE’) with positive, negative, and neutral affective content. We show that a select group of brain regions (PCC, precuneus, IPL, vACC) do exhibit activity that is greater during FIXATION (>PICTURE); these regions have previously been implicated in the “default brain network”. In addition, we report that activity within precuneus and IPL in the FIXATION period is attenuated by the precedent processing of images with positive and negative emotional content, relative to non-emotional content. These data suggest that the activity within regions implicated in the default network is modulated by the presence of environmental stimuli with motivational salience and, thus, adds to our understanding of the brain function during periods of low cognitive, emotional, or sensory demand.
fMRI; rest; baseline; fixation; emotion; affect; parietal cortex; precuneus
Neural and behavioral evidence for cortical reorganization in the adult somatosensory system after loss of sensory input (e.g., amputation) has been well documented. In contrast, evidence for reorganization in the adult visual system is far less clear: neural evidence is the subject of controversy, behavioral evidence is sparse, and studies combining neural and behavioral evidence have not previously been reported. Here, we report converging behavioral and neuroimaging evidence from a stroke patient (B.L.) in support of cortical reorganization in the adult human visual system. B.L.’s stroke spared the primary visual cortex (V1), but destroyed fibers that normally provide input to V1 from the upper left visual field (LVF). As a consequence, B.L. is blind in the upper LVF, and exhibits distorted perception in the lower LVF: stimuli appear vertically elongated, toward and into the blind upper LVF. For example, a square presented in the lower LVF is perceived as a rectangle extending upward. We hypothesized that the perceptual distortion was a consequence of cortical reorganization in V1. Extensive behavioral testing supported our hypothesis, and functional magnetic resonance imaging (fMRI) confirmed V1 reorganization. Together, the behavioral and fMRI data show that loss of input to V1 after a stroke leads to cortical reorganization in the adult human visual system, and provide the first evidence that reorganization of the adult visual system affects visual perception. These findings contribute to our understanding of the human adult brain’s capacity to change and has implications for topics ranging from learning to recovery from brain damage.
cortical reorganization; cortical plasticity; primary visual cortex; perceptual distortion; adult human visual system; visual perception
This study investigates the extent to which participants with major depression differ from healthy comparison participants in the irregularities in affective information processing, characterized by deficits in facial expression recognition, intensity categorization, and reaction time to identifying emotionally salient and neutral information. Data on diagnoses, symptom severity, and affective information processing using a facial recognition task were collected from 66 participants, male and female between ages 18 and 54 years, grouped by major depressive disorder (N = 37) or healthy nonpsychiatric (N = 29) status. Findings from MANCOVAs revealed that major depression was associated with a significantly longer reaction time to sad facial expressions compared with healthy status. Also, depressed participants demonstrated a negative bias towards interpreting neutral facial expressions as sad significantly more often than healthy participants. In turn, healthy participants interpreted neutral faces as happy significantly more often than depressed participants. No group differences were observed for facial expression recognition and intensity categorization. The observed effects suggest that depression has significant effects on the perceptivity of the intensity of negative affective stimuli, delayed speed of processing sad affective information, and biases towards interpreting neutral faces as sad.
affective information processing; facial; mood disorders
The prevalence of suicidal attempts and self-injurious behavior among 376 patients diagnosed with Intermittent Explosive Disorder (IED) was assessed via structured interviews. Results showed 16% of IED subjects reported self-aggression, with 12.5% reporting suicide attempts and 7.4% reporting non lethal self-injurious behaviors. Additional risk factors were identified.
Intermittent Explosive Disorder; Self-Injurious Behavior; Suicide Attempts
The moderating effects of depression on self-injurious behavior among personality-disordered individuals (N = 40) was examined. Self-injurious behavior (SIB) was assessed using a well-validated laboratory measure. Remitted depression was associated with greater sensitivity to self-aggressive cues, indicating that remitted depression may be a risk factor for SIB.
Depression; Self-Aggression; Personality Disorder
Antigen-evoked influx of extracellular Ca2+ into mast cells may occur via store-operated Ca2+ channels called calcium release–activated calcium (CRAC) channels. In mast cells of the rat basophilic leukemia cell line (RBL-2H3), cholera toxin (CT) potentiates antigen-driven uptake of 45Ca2+ through cAMP-independent means. Here, we have used perforated patch clamp recording at physiological temperature to test whether cholera toxin or its substrate, Gs, directly modulates the activity of CRAC channels. Cholera toxin dramatically amplified (two- to fourfold) the Ca2+ release–activated Ca2+ current (ICRAC) elicited by suboptimal concentrations of antigen, without itself inducing ICRAC, and this enhancement was not mimicked by cAMP elevation. In contrast, cholera toxin did not affect the induction of ICRAC by thapsigargin, an inhibitor of organelle Ca2+ pumps, or by intracellular dialysis with low Ca2+ pipette solutions. Thus, the activity of CRAC channels is not directly controlled by cholera toxin or Gsα. Nor was the potentiation of ICRAC due to enhancement of phosphoinositide hydrolysis or calcium release. Because Gs and the A subunit of cholera toxin bind to ADP ribosylation factor (ARF) and could modulate its activity, we tested the sensitivity of antigen-evoked ICRAC to brefeldin A, an inhibitor of ARF-dependent functions, including vesicle transport. Brefeldin A blocked the enhancement of antigen-evoked ICRAC without inhibiting ADP ribosylation of Gsα, but it did not affect ICRAC induced by suboptimal antigen or by thapsigargin. These data provide new evidence that CRAC channels are a major route for Fc∈ receptor I–triggered Ca2+ influx, and they suggest that ARF may modulate the induction of ICRAC by antigen.
mast cells; patch clamp; Ca2+ imaging; Gs; brefeldin A