Double dissociation in the anatomy of socioemotional disinhibition and executive functioning in dementia.

Objective: To determine whether socioemotional disinhibition and executive dysfunction are related to dissociable patterns of brain atrophy in neurodegenerative disease. Previous studies have indicated that behavioral and cognitive dysfunction in neurodegenerative disease are linked to atrophy in different parts of the frontal lobes, but these prior studies did not establish that these relationships were specific, which would best be demonstrated by a double dissociation. Method: Subjects included 157 patients with neurodegenerative disease. A semiautomated parcellation program (Freesurfer) was used to generate regional cortical volumes from structural MRI scans. Regions of interest (ROIs) included anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). Socioemotional disinhibition was measured using the Neuropsychiatric Inventory. Principal component analysis including 3 tasks of executive function (EF; verbal fluency, Stroop Interference, modified Trails) was used to generate a single-factor score to represent EF. Results: Partial correlations between ROIs, disinhibition, and EF were computed after controlling for total intracranial volume, Mini-Mental State Examination, diagnosis, age, and education. Brain regions significantly correlated with disinhibition (ACC, OFC, IFG, and temporal lobes) and EF (MFG) were entered into separate hierarchical regressions to determine which brain regions predicted disinhibition and EF. OFC was the only brain region to significantly predict disinhibition, and MFG significantly predicted EF performance. A multivariate general linear model demonstrated a significant interaction between ROIs and cognitive–behavioral functions. Conclusions: These results support a specific association between orbitofrontal areas and behavioral management as compared with dorsolateral areas and EF. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Neuropsychological correlates of short-term memory distractor tasks among patients with surgical repair of anterior communicating artery aneurysms.

The relative utility of the visual consonant trigram (VCT) and release from proactive inhibition (PI) versions of the short-term memory (STM) distractor task in investigating the separate but related cognitive realms of memory and executive frontal lobe functioning were explored in patients with anterior communicating artery (ACoA) aneurysms n?=?24. Compared with normal controls n?=?19, ACoA patients were impaired on clinical measures of memory and on measures of executive functioning, including concept formation and fluent word generation. Furthermore, ACoA patients were impaired on the VCT task but not on the release-from PI task, indicating a differential sensitivity of these tasks to the impairment manifested by ACoA patients. Regression modeling indicated that the VCT and release-from-PI tasks were closely associated with clinical memory tests, although the release-from-PI-task was also associated with fluency, an executive functioning domain. In general, our results fail to support the broad generalization that impaired performance on STM distractor tasks is necessarily symptomatic of frontal lobe dysfunction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence for executive dysfunction in autism

A group of young people with autism (ranging in ability from high functioning to moderately learning disabled), and ability-matched control groups of (i) non-autistic individuals with moderate learning disabilities, and (ii) normally developing children, were presented with two tests of executive function: the Intra-dimensional/Extra-dimensional set-shifting task and the Tower of London planning task. These tests were graded in difficulty and included internal control measures. On each task, the autistic group was differentially impaired with respect to both control groups. Moreover, this impairment was specific to the stages of each task which placed greatest demands upon executive control. This evidence for executive dysfunction in autism is discussed in the context of Norman and Shallice's (Centre for Human Information Processing Technical Report 99, 1980) "Supervisory Attentional System" model of frontal function.     

Event-Related fMRI Study of Context Processing in Dorsolateral Prefrontal Cortex of Patients With Schizophrenia.

Context processing is conceptualized as an executive function involved in voluntary, complex actions such as overcoming automatic responses. The present study tested the hypothesis that context-processing deficits in patients with schizophrenia are associated with a dysfunction of left dorsolateral prefrontal cortex (DLPFC). Using event-related functional magnetic resonance imaging (fMRI), 17 controls and 17 medicated patients performed a version of the AX task in which a learned, automatic response had to be inhibited. In controls, left DLPFC activity increased when preparing to overcome an automatic response, whereas patients with schizophrenia showed no differential activation. In controls, context processing appeared to be associated with the differential representation of cues associated with the need to provide top-down support for overcoming automatic responses. This mechanism appeared to be impaired in patients with schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Executive Functioning and Speed of Processing in Phenylketonuria.

Treated phenylketonuria (PKU) has been linked to dopaminergic depletion in the dorsolateral prefrontal cortex, potentially leading to selective executive impairment. White matter abnormalities may lead to generalized slowing of information processing. These 2 hypotheses were evaluated in adults with PKU on a lifelong diet. Those with PKU were significantly slower than the control group regardless of working memory load on an n-back task and marginally slower regardless of trial type (inhibitory or noninhibitory) on a flanker task. There were no significant differences in speed on object alternation learning or perceptual judgment tasks. There were no group differences in accuracy on any task. These findings do not appear consistent with the selective executive hypothesis. A cognitive slowing account may prove more informative in adults with PKU, but more evidence is needed. The findings suggest that continuous dietary management is a fairly successful strategy in terms of cognitive outcome for adults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal and spatial context memory in patients with focal frontal, temporal lobe, and diencephalic lesions

Patients with focal frontal, temporal lobe, or diencephalic lesions were investigated on measures of temporal (recency) and spatial (position) context memory, after manipulating exposure times to match recognition memory for targets (pictorial stimuli) as closely as possible. Patients with diencephalic lesions from an alcoholic Korsakoff syndrome showed significant impairment on the temporal context (recency) task, as did patients with frontal lesions penetrating the dorsolateral frontal cortex, according to MRI (and PET) evidence. Patients with temporal lobe lesions showed only a moderate (non-significant) impairment on this task, and patients with medial frontal lesions, or large frontal lesions not penetrating the dorsolateral cortical margins, performed as well as healthy controls at this task. On the spatial context memory task, patients with lesions in the temporal lobes showed significant impairment, and patients with right temporal lesions performed significantly worse than patients with left temporal lesions. Patients with diencephalic lesions showed only a modest (non-significant) impairment on this task, and the frontal lobe group performed normally. When a group of patients with temporal lobe lesions resulting from herpes encephalitis were examined separately, an identical pattern of results was obtained, the herpes group being significantly impaired on spatial memory and showing a trend towards impairment for temporal context memory. There were strong correlations between anterograde memory quotients and context memory performance (despite the use of an exposure time titration procedure) and a weak association in the frontal group with one frontal/executive task [corrected] (card-sorting perservations). It is predicted that correlations between temporal context memory and frontal/executive tasks will be greater in samples of patients all of whom have frontal lesions invading the dorsolateral cortical margin.     

Polymorphisms in dopamine system genes are associated with individual differences in attention in infancy.

Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine D4 receptor (DRD4) genes are likely to impact directly on the functioning of the frontal cortex, whereas polymorphisms in the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes might influence frontal cortex functioning indirectly via strong frontostriatal connections. A significant effect of the COMT valine1??methionine (Val158Met) polymorphism was found. Infants with the Met/Met genotype were significantly less distractible than infants with the Val/Val genotype in Freeze-Frame trials presenting an engaging central stimulus. In addition, there was an interaction with the DAT1 3` variable number of tandem repeats polymorphism; the COMT effect was present only in infants who did not have two copies of the DAT1 10-repeat allele. These findings indicate that dopaminergic polymorphisms affect selective aspects of attention as early as infancy and further validate the Freeze-Frame task as a frontal cortex task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recollection- and familiarity-based memory in healthy aging and amnestic mild cognitive impairment.

Little is known about the cognitive mechanisms of the memory impairment associated with amnestic mild cognitive impairment (aMCI). We explored recollection and familiarity in 27 healthy young adults, 45 healthy older adults, and 17 individuals with aMCI. Relative to the younger adults, recollection was reduced in the older adults, especially among those with aMCI. Familiarity did not differ among groups. In the healthy younger and older adults, better performance on a set of clinical memory measures that are sensitive to medial temporal lobe functioning was associated with greater recollection. In addition, among the healthy older adults better executive functioning was also associated with greater recollection. These results are consistent with the notion that recollection is a product of strategic processes mediated by the prefrontal cortex that suppport the retrieval of context-dependent memories from the hippocampus. Hippocampal atrophy associated with aMCI may disrupt this brain network, and thereby interfere with recollection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sensitivity to Expectancy Violations in Healthy Aging and Mild Cognitive Impairment.

In this study, individuals with mild cognitive impairment (MCI) were tested to see if executive dysfunction impacts their implementation of expectancy biases in a priming task. Young adults, healthy older adults, and individuals with MCI made speed-related decisions to sequentially presented word pairs. The proportion of category related (e.g., apple-fruit) versus coordinate related (apple-pear) pairs was varied to create different expectancy biases. When the proportion of category pairs was high (80%), the control groups showed an expectancy bias: Significant inhibition was observed for coordinate pairs compared with category pairs. The MCI group also demonstrated an expectancy bias but with much larger costs for unexpected targets. The findings suggest that individuals with MCI are inordinately sensitive to expectancy violations, and these findings are discussed in terms of possible executive dysfunction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impairment in object-in-place scene learning after uncinate fascicle section in macaque monkeys.

Three previous experiments have shown that a disconnection of frontal cortex from inferior temporal cortex in monkeys impairs a variety of visual learning tasks but leaves concurrent object discrimination learning intact. In the present experiment, three monkeys were trained on an object-in-place task where concurrent object discrimination learning took place within unique background scenes. After surgery to transect the uncinate fascicle, the monosynaptic route between prefrontal cortex and inferior temporal cortex, all three monkeys showed an impairment relative to their preoperative performance. Combined with previously reported impairments after uncinate fascicle transection, the interaction between frontal cortex and inferotemporal cortex is likely to be important in discrimination learning in background scenes because learning depends on associating the visual elements of a scene together with the appropriate choice object. This result adds to recent evidence showing that tasks such as object-in-place learning and conditional learning are impaired after disconnection of frontal cortex from inferior temporal cortex because those tasks require the representation of temporally extended events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A differential deficit in time- versus event-based prospective memory in Parkinson's disease.

Objective: The aim of the current study was to clarify the nature and extent of impairment in time- versus event-based prospective memory in Parkinson's disease (PD). Prospective memory is thought to involve cognitive processes that are mediated by prefrontal systems and are executive in nature. Given that individuals with PD frequently show executive dysfunction, it is important to determine whether these individuals may have deficits in prospective memory that could impact daily functions, such as taking medications. Although it has been reported that individuals with PD evidence impairment in prospective memory, it is still unclear whether they show a greater deficit for time- versus event-based cues. Method: Fifty-four individuals with PD and 34 demographically similar healthy adults were administered a standardized measure of prospective memory that allows for a direct comparison of time-based and event-based cues. In addition, participants were administered a series of standardized measures of retrospective memory and executive functions. Results: Individuals with PD demonstrated impaired prospective memory performance compared to the healthy adults, with a greater impairment demonstrated for the time-based tasks. Time-based prospective memory performance was moderately correlated with measures of executive functioning, but only the Stroop Neuropsychological Screening Test emerged as a unique predictor in a linear regression. Conclusions: Findings are interpreted within the context of McDaniel and Einstein's (2000) multiprocess theory to suggest that individuals with PD experience particular difficulty executing a future intention when the cue to execute the prescribed intention requires higher levels of executive control. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Positive mood and executive function: Evidence from Stroop and fluency tasks.

Contrasting predictions have been made about the effects of positive mood states on the performance of frontal lobe tests that tap executive functions such as inhibition, switching, and strategy use. It has been argued that positive mood is likely to improve some cognitive processes, particularly those dependent on the frontal cortex and anterior cingulate of the brain. However, there is some evidence that happy mood may impair executive functioning. The current experiments investigated the effects of positive mood on Stroop and fluency tests, which are frequently used to assess executive function. Positive mood impaired performance on a switching condition of the Stroop test, but improved performance on a creative uses test of fluency. The effect of positive mood on an executive task may therefore depend on whether a task is inherently motivating or is impaired by diffuse semantic activation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired reversal but intact acquisition: Probabilistic response reversal deficits in adult individuals with psychopathy.

The performance of adult psychopathic individuals on a novel response reversal task involving 2 reward-punishment contingencies (100-0 and 80-20) was investigated. In line with predictions, adults with psychopathy presented with impairment on the response reversal component but not on the acquisition component of this task. This selective impairment for response reversal was seen for both reward-punishment contingencies and was related to the tendency of individuals with psychopathy to be less likely to stay with a rewarded correct response to a stimulus on the subsequent presentation of that stimulus. Results are discussed with reference to current models of the development of psychopathy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prefrontal Brain Magnetic Activity: Effects of Memory Task Demands.

Changes in spatiotemporal profiles of brain magnetic activity were investigated in healthy volunteers as a function of varying demands for phonological storage of spoken pseudowords. Greater activity for the phonological memory task was restricted to the dorsolateral prefrontal cortex (DLPFC) in the left hemisphere. During performance of the memory task, activity was initially found in the left superior temporal gyrus (between 100 and 200 ms), followed by activity in the ventrolateral prefrontal, motor, and premotor cortices (between 200 and 300 ms). Activity in DLPFCs was first observed consistently across participants later, between 300 and 400 ms. The data are consistent with the purported role of posterior temporal cortices in phonological analysis and in the online storage of phonological information, the contribution of ventrolateral and motor processing areas in establishment and short-term maintenance of articulatory representations through rehearsal, and the role of DLPFCs in the executive control of the maintenance operation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Frontal lobe functions in psychopaths.

Hypothesized that psychopaths would exhibit deficits on tasks tapping the frontal lobe functions of cognitive flexibility and perseverance. 20 male psychopaths (mean age 26.5 yrs), 23 male psychiatric controls, and 18 normal male controls (18–20 yrs old) completed the Socialization scale of the California Psychological Inventory, a behavioral checklist, and a task battery. Relative to controls, psychopaths exhibited the performance pattern of frontal lesion patients on all measures empirically related to frontal dysfunction: perseverative errors on the Wisconsin Card Sorting Task, errors on a sequential matching memory task, and Necker Cube reversals. Results encourage the pursuit of a conceptualization of psychopathy based on deficits in cognitive functions previously associated with frontal lobe. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prefrontal cortex and rule abstraction: Where and whether? Theoretical comment on Moore et al. (2009).

The primate dorsolateral prefrontal cortex is implicated in diverse aspects of behavioral regulation, cognitive control, and memory. However, direct neuropsychological evidence supporting a requirement of this area in functions other than spatial working memory has been scarce. T. L. Moore, S. P. Schettler, R. J. Killiany, D. L. Rosene, and M. B. Moss (see record 2009-04037-001) have shown, for the first time, that lesions of dorsolateral prefrontal cortex in the rhesus monkey (including areas 9 and 46) substantially impair performance in a test of executive function modeled on the Wisconsin Card Sorting Task. The pattern of impairment is consistent with a role for dorsolateral prefrontal areas in rule abstraction but may relate to a role for this area in rule maintenance as well. Interestingly, monkeys with dorsolateral prefrontal lesions do not appear to perseverate in their use of particular rules in the task, different from the common impairment associated with frontal lobe damage in humans. These findings indicate that dorsolateral prefrontal cortex is necessary for some aspects of rule-guided behavior in the primate brain and help illuminate the involvement of different prefrontal areas in different aspects of executive function and rule-guided behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Instrumental learning and relearning in individuals with psychopathy and in patients with lesions involving the amygdala or orbitofrontal cortex.

Previous work has shown that individuals with psychopathy are impaired on some forms of associative learning, particularly stimulus-reinforcement learning (Blair et al., 2004; Newman & Kosson, 1986). Animal work suggests that the acquisition of stimulus-reinforcement associations requires the amygdala (Baxter & Murray, 2002). Individuals with psychopathy also show impoverished reversal learning (Mitchell, Colledge, Leonard, & Blair, 2002). Reversal learning is supported by the ventrolateral and orbitofrontal cortex (Rolls, 2004). In this paper we present experiments investigating stimulus-reinforcement learning and relearning in patients with lesions of the orbitofrontal cortex or amygdala, and individuals with developmental psychopathy without known trauma. The results are interpreted with reference to current neurocognitive models of stimulus-reinforcement learning, relearning, and developmental psychopathy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Karl Landsteiner, the melancholy genius: his time and his colleagues, 1868-1943

Object alternation (OA) is a well-established measure of perseveration and orbitofrontal function in non-human primates. Although several studies have used OA to examine orbitofrontal system dysfunction in humans with neurological and psychiatric disease, this task itself has not been validated as a bona fide measure of frontal dysfunction in humans. To address this issue, six patients with bilateral frontal lobe lesions documented by computerized tomography (CT) or magnetic resonance imaging (MRI) and 15 healthy controls were given OA, as well as other measures of frontal system dysfunction, delayed alternation (DA), delayed response (DR), and the Wisconsin Card Sorting Test (WCST). The CT and MRI scans were interpreted blindly. The patients with bilateral frontal lesions were significantly impaired on OA, DA, DR and the WCST. Analyses of the CT/MRI lesions suggest that the neuroanatomical regions involved in the deficits on OA include Brodmann areas 10, 24, 32 and 47, as well as possibly 11, and that OA is a sensitive measure of ventrolateral-orbitofrontal and medial frontal dysfunction in humans. Our findings lend further support for the use of experimental paradigms adopted from animal models to study the functional neuroanatomy and neuropsychological mechanisms underlying cognitive functions in humans with neurological and psychiatric disease.     

Dynamic variation in pleasure in children predicts nonlinear change in lateral frontal brain electrical activity.

Individual variation in the experience and expression of pleasure may relate to differential patterns of lateral frontal activity. Brain electrical measures have been used to study the asymmetric involvement of lateral frontal cortex in positive emotion, but the excellent time resolution of these measures has not been used to capture second-by-second changes in ongoing emotion until now. The relationship between pleasure and second-by-second lateral frontal activity was examined with the use of hierarchical linear modeling in a sample of 128 children ages 6–10 years. Electroencephalographic activity was recorded during “pop-out toy,” a standardized task that elicits pleasure. The task consisted of 3 epochs: an anticipation period sandwiched between 2 play periods. The amount of pleasure expressed during the task predicted the pattern of nonlinear change in lateral frontal activity. Children who expressed increasing amounts of pleasure during the task exhibited increasing left lateral frontal activity during the task, whereas children who expressed contentment exhibited increasing right/decreasing left activity. These findings indicate that task-dependent changes in pleasure relate to dynamic, nonlinear changes in lateral frontal activity as the task unfolds. (PsycINFO Database Record (c) 2010 APA, all rights reserved)