Developmental outcomes after early prefrontal cortex damage

The neuropsychological bases of cognitive, social, and moral development are minimally understood, with a seemingly wide chasm between developmental theories and brain maturation models. As one approach to bridging ideas in these areas, we review 10 cases of early prefrontal cortex damage from the clinical literature, highlighting overall clinical profiles and real life developmental outcomes. Based on these cases, there is preliminary evidence to support distinctive developmental differences after: (1) dorsolateral, (2) mesial, and (3) orbital-polar prefrontal lesions, for more profound impairments after bilateral damage, and possibly for recovery differences after very early vs. later childhood lesion onset. Further case and group studies are needed to confirm reliable effects of specific lesion locations, the influence of age of lesion onset, and related experiential and treatment variables in determining adult outcomes. Rather than a single underlying deficit associated with early prefrontal cortex damage, we interpret the findings to suggest that it is the altered integration and interplay of cognitive, emotional, self-regulatory, and executive/metacognitive deficits that contribute to diverse developmental frontal lobe syndromes. The findings support the fundamental importance of prefrontal cortex maturation in protracted cognitive, social-emotional, and moral development.     

Multidimensional assessment of empathic abilities in patients with insular glioma

Recent studies have provided evidence that there are two possible systems for empathy: affective empathy (AE) and cognitive empathy (CE). Neuroimaging paradigms have proven that the insular cortex is involved in empathy processing, particularly in AE. However, these observations do not provide causal evidence for the role of the insula in empathy. Although impairments in empathy have been described following insular damage in a few case studies, it is not clear whether insular cortex is involved in CE and whether these two systems are impaired independently or laterally in patients with insular gliomas. In this study, we assessed 17 patients with an insular glioma, 17 patients with a noninsular glioma, and 30 healthy controls using a method that combined a self-report empathy questionnaire with the emotion recognition task, assessment of empathy for others’ pain, and the emotional perspective-taking paradigm. We found that patients with an insular glioma had lower scores for empathic concern and perspective taking than did either healthy controls or lesion controls. The patients’ abilities to recognize facial emotions, perceive others’ pain, and understand the emotional perspectives of others were also significantly impaired. Furthermore, we did not observe a laterality effect on either AE or CE among those with insular lesions. These findings revealed that both AE and CE are impaired in patients with an insular glioma and that the insular cortex may be a central neuroanatomical structure in both the AE and CE systems.     

Effect of prefrontal cortex damage on resolving lexical ambiguity in text

The function of suppression of context-inappropriate meanings during lexical ambiguity resolution was examined in 25 adults with prefrontal cortex damage (PFCD) localized to the left (N=8), right (N=6), or bilaterally (N=11); and 21 matched Controls. Results revealed unexpected inverse patterns of suppression between PFCD and Control groups, with measures suggesting decreased interference across time in the PFCD group and increased interference in the Control group. The PFCD group, however, had significantly lower accuracy rates for the context-inappropriate condition. Results suggest a loss of the control aspects of inhibitory processes in lexical ambiguity resolution following PFCD. An aging effect on suppression function is also suggested.     

Preserved and impaired task-switching abilities in non-demented patients with Parkinson's disease

Existing studies on task switching in Parkinson's disease (PD) patients have led to somewhat different results. In particular, it is unclear whether PD patients have a deficit in attentional control. In this study, we assessed task-switching abilities in samples of non-demented PD patients and elderly controls. We used a paradigm in which there was a random task sequence and the task was cued in every trial. This allowed the investigation of both task-set reconfiguration and task-set dissipation. In terms of the proportion of errors made, the patients showed increased switch cost and congruency effects. For reaction times, PD patients showed enlarged congruency effects on switch trials, specifically in the condition in which we used a short constant response-cue interval (RCI). Nevertheless, in a similar fashion to older controls, the patients showed reductions in reaction time switch cost from a short to a long cue-target interval (CTI) and from a short to a long RCI. While these latter findings, respectively, suggest unimpaired task preparation and task dissipation on correct trials in the PD patients, the overall results show that they have a deficit in biasing and selecting currently relevant task sets and more generally argue in favour of a failure of attentional control in PD.     

Insensitivity to future consequences following damage to human prefrontal cortex

Following damage to the ventromedial prefrontal cortex, humans develop a defect in real-life decision-making, which contrasts with otherwise normal intellectual functions. Currently, there is no neuropsychological probe to detect in the laboratory, and the cognitive and neural mechanisms responsible for this defect have resisted explanation. Here, using a novel task which simulates real-life decision-making in the way it factors uncertainty of premises and outcomes, as well as reward and punishment, we find that prefrontal patients, unlike controls, are oblivious to the future consequences of their actions, and seem to be guided by immediate prospects only. This finding offers, for the first time, the possibility of detecting these patients' elusive impairment in the laboratory, measuring it, and investigating its possible causes.     

Long-term effect of prefrontal lobotomy on verbal fluency in patients with schizophrenia

OBJECTIVE: This study investigated the long-term effects of bilateral prefrontal leukotomy on lexical abilities in schizophrenia subjects. METHOD: we compared performances of leukotomized (LSP), non-leukotomized schizophrenia patients (NLSP) and normal controls, using a test of verbal fluency. Multiple case and triple comparison design were implemented. i.e., the performance of each LSP was compared to that of NLSP and that of a normal control. The sample consisted of four LSP, four NLSP, and four normal subjects. Subjects were matched in sex, age, handedness, and schooling. In Addition, schizophrenia groups were matched in diagnosis and years of hospitalization. Quantitative and qualitative analyses of generated words and errors produced by subjects were carried out. RESULTS: A deficiency in both groups of schizophrenia was observed, although a better performance in LSP patients was detected. CONCLUSION: Intact Lexical ability in LSP indicates its poor relation to the frontal lobe.     

Visual-perceptual abilities in healthy controls, depressed patients, and schizophrenia patients

Previous studies have suggested a right hemineglect in schizophrenia, however few assessed possible visual-perceptual implication in this lateralized anomaly. A manual line bisection without (i.e., lines presented on their own) or with a local cueing paradigm (i.e., a number placed at one or both ends of the line) and the Motor-free Visual Perceptual Test-Vertical format (MVPT-V) were used to assess the visual-perceptual abilities of healthy controls, schizophrenia and depressed patients. Whereas healthy controls and depressed patients showed a non-significant leftward bias in manual line bisection, schizophrenia patients bisected significantly to the left of the true centre of the line. Interestingly, the pattern of performances in response to the local cueing paradigm was similar in depressed and schizophrenia patients such that both groups demonstrated a significant change in their bisection performance only in response to a cue placed at the right extremity of the line (control performance was modified by cues at either end of the line). Finally, in the MVPT-V, schizophrenia patients were impaired relative to the other two groups, especially in the spatial working memory and visual closure categories. These results suggest that: 1/a deficit towards the right hemifield, consistent with a mild form of right hemineglect, can be observed in schizophrenia; 2/lateralized anomalies could also be observed in depression using an appropriate tool such as manual line bisection; 3/performances in the MVPT-V suggested that a simple visual-perceptual deficit could not explain the lateralized anomaly observed in the manual line bisection, as it is the case in the hemineglect syndrome.     

Associative learning impairments in patients with frontal lobe damage

The performance of 18 frontal lobe lesion (FL) and 10 frontal lobe dementia (FLD) patients on an associative memory test was compared with the performance of their matched normal controls. The FL group was severely impaired on cued and free recall and was moderately impaired on a recognition condition. Left FL patients performed the poorest on the cued and free recall conditions. The FLD patients were moderately impaired on the free recall condition only but there was a subgroup of FLD patients with additional left temporal atrophy who appeared severely impaired on both cued and free recall. These findings indicate that both left frontal and temporal lobe damage can impair associative learning and that this impairment is more strikingly seen with free rather than cued recall.     

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.     

Inhibitory attentional control in patients with frontal lobe damage

The performance of a group of frontal lobe lesion and a group of frontal lobe dementia patients was compared with the performance of their respective matched normal control groups on two tests of inhibitory attentional control-the stop-signal reaction time task and a negative priming task. Both patient groups responded significantly slower than their respective normal control groups, but they showed only marginally significant selective impairments on the measures of inhibition. The data suggest that the specific inhibitory processes evaluated by these two tests are, in general, spared in patients with focal frontal lobe lesions or frontal lobe degeneration.     

A Voxel-based lesion study on facial emotion recognition after circumscribed prefrontal cortex damage

Previous studies have shown inconsistent findings regarding the contribution of the different prefrontal regions in emotion recognition. Moreover, the hemispheric lateralization hypothesis posits that the right hemisphere is dominant for processing all emotions regardless of affective valence, whereas the valence specificity hypothesis posits that the left hemisphere is specialized for processing positive emotions while the right hemisphere is specialized for negative emotions. However, recent findings suggest that the evidence for such lateralization has been less consistent. In this study, we investigated emotion recognition of fear, surprise, happiness, sadness, disgust, and anger in 30 patients with focal prefrontal cortex lesions and 30 control subjects. We also examined the impact of lesion laterality on recognition of the six basic emotions. The results showed that compared to control subjects, the frontal subgroups were impaired in recognition of three negative basic emotions of fear, sadness, and anger – regardless of the lesion laterality. Therefore, our findings did not establish that each hemisphere is specialized for processing specific emotions. Moreover, the voxel-based lesion symptom mapping analysis showed that recognition of fear, sadness, and anger draws on a partially common bilaterally distributed prefrontal network.     

Evaluation of narrative abilities in patients suffering from Duchenne Muscular Dystrophy

The present work investigated cognitive, linguistic and narrative abilities in a group of children suffering from Duchenne Muscular Dystrophy, an allelic X-linked recessive disorder caused by mutations in the gene encoding dystrophin. The patients showed mildly reduced IQ with lower Verbal than Performance Intelligence Quotient and were mildly affected in visual attention and short-term memory processing. At the linguistic assessment, neither receptive (word comprehension) nor expressive (naming tasks and fluency) lexical abilities were impaired. However, their narratives were qualitatively inferior with respect to those produced by a group of typically developing children. Their speech samples were characterized by the presence of fewer verbs and complete sentences. It is suggested that the reduced production of complete sentences is due to a selective problem in verb argument structure generation. Since the lack of dystrophin is assumed to produce effects on the maturation of the cerebellum, whose involvement has been recently suggested in verb and syntactic processing, these findings may lend indirect support to the hypothesis of a cerebellar-cortical circuit specialized in verb and sentence production.     

Numerical approximation abilities correlate with and predict informal but not formal mathematics abilities

Previous research has found a relationship between individual differences in children’s precision when nonverbally approximating quantities and their school mathematics performance. School mathematics performance emerges from both informal (e.g., counting) and formal (e.g., knowledge of mathematics facts) abilities. It remains unknown whether approximation precision relates to both of these types of mathematics abilities. In the current study, we assessed the precision of numerical approximation in 85 3- to 7-year-old children four times over a span of 2 years. In addition, at the final time point, we tested children’s informal and formal mathematics abilities using the Test of Early Mathematics Ability (TEMA-3). We found that children’s numerical approximation precision correlated with and predicted their informal, but not formal, mathematics abilities when controlling for age and IQ. These results add to our growing understanding of the relationship between an unlearned nonsymbolic system of quantity representation and the system of mathematics reasoning that children come to master through instruction.     

Task-switching abilities in children with autism spectrum disorder

Task-switching performance is often used as a measure of executive control functions. Various task-switching studies in children with autism spectrum disorder (ASD) found, in contrast to expectations, no impairments in cognitive flexibility. Here, we studied whether the role of memory for arbitrary task rules can explain these findings, and how studying rule memory can help to generally better understand executive control. We designed a novel task-switching paradigm to separate cognitive flexibility from demand on memory for arbitrary rules, and we compared 19 children with ASD (9 to 16 years old) with an age- and IQ-matched control group. Children with ASD had increased difficulty with task switching only when memorizing arbitrary rules was required. When no arbitrary rules needed to be memorized, they performed accurately and quickly. Nevertheless, they showed less distraction from task-irrelevant stimulus features, suggesting that they represented tasks differently from the children in the comparison group. We conclude that children with ASD have a weaker capacity of forming rule representations, which only leads to performance impairment when they need to memorize arbitrary rules. Further, executive control impairments in ASD seem more complex than hitherto hypothesized due to mutual interactions between memory demand and task representations.     

Metamemory knowledge and beliefs in patients with schizophrenia and how these relate to objective cognitive abilities

Subjective reports and theories about memory may have an influence on other beliefs and behaviours. Patients with schizophrenia suffer a wide range of deficits affecting their awareness of daily life, including memory. With the Metamemory Inventory in Adulthood (MIA) we ascertained patients’ memory knowledge and thoughts about their own cognitive capacities and about several aspects of cognitive functioning: personal capacities, knowledge of processes, use of strategies, perceived change with ageing, anxiety, motivation and mastery. The participants’ ratings were correlated with their intellectual, cognitive and psychiatric data. Patients felt they had a lower capacity and marginally lower mastery over their memory than comparison subjects. They reported less recourse to strategies, and higher levels of memory-related anxiety. However, their knowledge of basic memory processes, motivation to succeed, and perception of ageing effects were similar. So patients with schizophrenia do not suffer a general and non specific impairment of their metacognitive knowledge.     

Reduced phonological similarity effects in patients with damage to the cerebellum

Ten cerebellar patients were compared to 10 control subjects on a verbal working memory task in which the phonological similarity of the words to be remembered and their modality of presentation were manipulated. Cerebellar patients demonstrated a reduction of the phonological similarity effect relative to controls. Further, this reduction did not depend systematically upon the presentation modality. These results first document that qualitative differences in verbal working memory may be observed following cerebellar damage, indicating altered cognitive processing, even though behavioral output as measured by the digit span may be within normal limits. However, the results also present problems for the hypothesis that the cerebellar role is specifically associated with articulatory rehearsal as conceptualized in the Baddeley-Hitch model of working memory.