The special involvement of the rostrolateral prefrontal cortex in planning abilities: an event-related fMRI study with the Tower of London paradigm

Planning abilities are essential for the successful management of everyday life activities. Although several neuroimaging studies provide evidence that the prefrontal cortex is crucially involved in planning, the differential roles of its subregions are still a matter of debate. The aim of this study was to investigate the neural correlates of planning by focusing on the functional differentiation between the dorsolateral and rostrolateral prefrontal cortex using the Tower of London (ToL) task and a parametric event-related functional MRI design. In order to control for activations unspecific to planning, two control conditions were presented, which were matched for the length of single events in the ToL task. Seventeen right-handed healthy subjects participated in this study. All statistics were reported with corrections for multiple comparisons (p < 0.05). Compared to control conditions, activations in the ToL task were observed in the dorsolateral prefrontal cortex bilaterally, the right ventrolateral and left rostrolateral prefrontal cortex along with the thalamus, as well as in the parietal and premotor cortex bilaterally. Task complexity dependent analyses revealed that only the left rostrolateral prefrontal cortex showed a BOLD signal increase over the four planning levels, which could not be observed in the control conditions. Hence, current findings suggest that planning involves an extensive fronto-parieto-thalamic network. Within this network, the rostrolateral prefrontal cortex seems to be the only region that is exclusively reactive to planning specific processes, which we described in terms of simultaneous monitoring of internally generated and externally presented information.     

Dissociating age-related changes in cognitive strategy and neural efficiency using event-related fMRI

We used event-related fMRI to measure brain activity while younger and older adults performed an item-recognition task in which the memory-set size varied between 1 and 8 letters. Each trial was composed of a 4-second encoding period in which subjects viewed random letter strings, a 12-second retention period and a 2-second retrieval period in which subjects decided whether a single probe letter was or was not part of the memory set. For both groups, reaction time increased and accuracy decreased with increasing memory set-size. There were minimal age-related differences in activation patterns with increasing memory set-size in prefrontal cortex (PFC). Regression analyses of individual subjects' performance and cortical activity indicated that speed and accuracy accounted for considerable variance in dorsal and ventral PFC activity during encoding and retrieval. These results suggest that younger and older adults utilize similar working memory (WM) strategies to accommodate increasing memory demand. They support a model of cognitive slowing in which processing rate is related to neural efficiency.     

Stroop performance in bipolar disorder: further evidence for abnormalities in the ventral prefrontal cortex

OBJECTIVES: Bipolar patients are impaired in Stroop task performance, a measure of selective attention. Structural and functional abnormalities in task-associated regions, in particular the prefrontal cortex (PFC), have been reported in this population. We aimed to examine the relationship between functional abnormalities, impaired task performance and the severity of depressive symptoms in bipolar patients. METHODS: Remitted bipolar patients (n = 10; all medicated), either euthymic or with subsyndromal depression, and age-matched control subjects (n = 11) viewed 10 alternating blocks of incongruent Stroop and control stimuli, naming the colour of the ink. Neural response was measured using functional magnetic resonance imaging. We computed between-group differences in neural response and within-group correlations with mood and anxiety. RESULTS: There were no significant between-group differences in task performance. During the Stroop condition, controls demonstrated greater activation of visual and dorsolateral and ventrolateral prefrontal cortical areas; bipolar patients demonstrated relative deactivation within orbital and medial prefrontal cortices. Depression scores showed a trend towards a negative correlation with the magnitude of orbitofrontal cortex deactivation in bipolar patients, whereas state anxiety correlated positively with activation of dorsolateral PFC and precuneus in controls. CONCLUSIONS: Our findings confirm previous reports of decreased ventral prefrontal activity during Stroop task performance in bipolar patients, and suggest a possible negative correlation between this and depression severity in bipolar patients. These findings further highlight the ventromedial PFC as a potential candidate for illness related dysfunction in bipolar disorder.     

Altered Prefrontal and Hippocampal Function During Verbal Encoding and Recognition in People With Prodromal Symptoms of Psychosis

Despite robust evidence of hippocampal abnormalities in schizophrenia, it is unclear whether hippocampal dysfunction predates the onset of psychosis. We used functional magnetic resonance imaging to investigate hippocampal function in subjects with an at-risk mental state (ARMS). Eighteen subjects meeting criteria for an ARMS and 22 healthy controls, matched for age, gender, and premorbid IQ, were scanned while performing a version of the Deese-Roediger-McDermott false memory task. During an encoding phase, subjects read lists of words aloud. Following a delay, they were presented with 24 target words, 24 semantically related lure words, and 24 novel words and required to indicate if each had been presented before. Behaviorally, the ARMS group made more false alarm responses for novel words than controls (P = .04) and had a lower discrimination accuracy for target words (P = .02). During encoding, ARMS subjects showed less activation than healthy controls in the left middle frontal gyrus, the bilateral medial frontal gyri, and the left parahippocampal gyrus. Correct recognition relative to false alarms was associated with differential engagement of the hippocampus bilaterally in healthy controls, but this difference was absent in the ARMS group. The ARMS was associated with altered function in the medial temporal cortex, as well as in the prefrontal regions, during both verbal encoding and recognition. These neurofunctional differences were associated with diminished recognition performance and may reflect the greatly increased risk of psychosis associated with the ARMS.     

Semantic and syntactic processing in Chinese sentence comprehension: evidence from event-related potentials

An ERP experiment was conducted to explore semantic and syntactic processes as well as their interplay in Chinese sentence comprehension. Participants were auditorily presented with Chinese ba sentences, which were either correct, semantically incorrect, syntactically incorrect, or both semantically and syntactically incorrect. The syntactic violation, which was created by eliminating the object-noun phrase from a preposition-object phrase structure, elicited an early starting anterior negativity which merged into a sustained negativity over anterior sites and a temporally limited centro-parietal negativity. The semantic violation elicited an early starting N400 effect. The combined violation in which the syntactic phrase structure violation and the semantic violation were crossed elicited an early staring sustained anterior negativity similar to the pure syntactic effect, and a centro-parietal negativity which was more negative than those of the syntactic condition and the semantic condition. No P600 was obtained neither for the syntactic nor for the combined condition. The results suggest that the syntactic processes (at about 50 ms) appear earlier than the semantic processes (at around 150 ms). They are independent from each other in the early time window (150-250 ms) but interact in a later processing phase (250-400 ms) during Chinese ba sentence comprehension. The broadly distributed negativity, which occurred during the N400 latency range observed in the three violation conditions, is thought to reflect thematic integration processes in the sentence-final position.     

Behavioral conflict, anterior cingulate cortex, and experiment duration: implications of diverging data

We investigated the relationship between behavioral measures of conflict and the degree of activity in the anterior cingulate cortex (ACC). We reanalyzed an existing data set that employed the Stroop task using functional magnetic resonance imaging [Milham et al., Brain Cogn 2002;49:277-296]. Although we found no changes in the behavioral measures of conflict from the first to the second half of task performance, we found a reliable reduction in the activity of the anterior cingulate cortex. This result suggests the lack of a strong relationship between behavioral measurements of conflict and anterior cingulate activity. A concomitant increase in dorsolateral prefrontal cortex activity was also found, which may reflect a tradeoff in the neural substrates involved in supporting conflict resolution, detection, or monitoring processes. A second analysis of the data revealed that the duration of an experiment can dramatically affect interpretations of the results, including the roles in which particular regions are thought to play in cognition. These results are discussed in relation to current conceptions of ACC's role in attentional control. In addition, we discuss the implication of our results with current conceptions of conflict and of its instantiation in the brain. Hum. Brain Mapping 21:96-105, 2004.     

The attenuation of dysfunctional emotional processing with stimulant medication: An fMRI study of adolescents with ADHD

Functional neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have focused on the neural correlates of cognitive control. However, for many youths with ADHD, emotional lability is an important clinical feature of the disorder. We aimed to identify the neural substrates associated with emotional lability that were distinct from impairments in cognitive control and to assess the effects that stimulants have on those substrates. We used functional magnetic resonance imaging (fMRI) to assess neural activity in adolescents with (N = 15) and without (N = 15) ADHD while they performed cognitive and emotional versions of the Stroop task that engage cognitive control and emotional processing, respectively. The participants with ADHD were scanned both on and off stimulant medication in a counterbalanced fashion. Controlling for differences in cognitive control, we found that during the emotional Stroop task, adolescents with ADHD as compared with controls demonstrated atypical activity in the medial prefrontal cortex (mPFC). Stimulants attenuated activity in the mPFC to levels comparable with controls.     

Functional brain activation during arithmetic processing in females with fragile X Syndrome is related to FMR1 protein expression

Arithmetic processing deficits in persons with fragile X Syndrome (fraX), the most common heritable cause of mental retardation, are well known. In this study, we characterize the neural underpinnings of these performance deficits using functional MRI. Given that a single gene defect (FMR1) is known to be responsible for this disorder, we also assess whether brain activation in arithmetic processing areas is related to amount of FMR1 protein expression (FMRP). Subjects included 16 females with fraX, and 16 female age-matched controls. Subjects viewed arithmetic equations with two (1 + 3 = 4) or three (2 + 3 - 1 = 5) operands, and were asked to judge whether the results were correct or not. Subjects with fraX showed significant impairment in behavioral performance on the 3-operand but not the 2-operand arithmetic equations. Significant brain activation was observed bilaterally in the prefrontal and parietal cortices for unaffected subjects, and bilateral prefrontal and left angular gyrus for subjects with fraX, for both trial types. Subjects with fraX exhibited less overall activation than did unaffected subjects in both types of trials; and, unlike the unaffected group, did not show increased extent of activation in association with greater task difficulty. During the 3-operand trials, activation in bilateral prefrontal and motor/premotor, and left supramarginal and angular gyri were positively correlated with FMRP, suggesting that decreased FMR1 protein expression underlies deficits in math performance in persons with fraX. More broadly, this investigation demonstrates a unique bridging of cognitive and molecular neuroscience and represents a useful approach for the study of brain development and function.     

Processing concrete words: fMRI evidence against a specific right-hemisphere involvement

Behavioral, patient, and electrophysiological studies have been taken as support for the assumption that processing of abstract words is confined to the left hemisphere, whereas concrete words are processed also by right-hemispheric brain areas. These are thought to provide additional information from an imaginal representational system, as postulated in the dual-coding theory of memory and cognition. Here we report new event-related fMRI data on the processing of concrete and abstract words in a lexical decision task. While abstract words activated a subregion of the left inferior frontal gyrus (BA 45) more strongly than concrete words, specific activity for concrete words was observed in the left basal temporal cortex. These data as well as data from other neuroimaging studies reviewed here are not compatible with the assumption of a specific right-hemispheric involvement for concrete words. The combined findings rather suggest a revised view of the neuroanatomical bases of the imaginal representational system assumed in the dual-coding theory, at least with respect to word recognition.     

Prefrontal cortex involvement in creative problem solving in middle adolescence and adulthood

Creative cognition, defined as the generation of new yet appropriate ideas and solutions, serves important adaptive purposes. Here, we tested whether and how middle adolescence, characterized by transformations toward life independency and individuality, is a more profitable phase than adulthood for creative cognition. Behavioral and neural differences for creative problem solving in adolescents (15–17 years) and adults (25–30 years) were measured while performing a matchstick problem task (MPT) in the scanner and the creative ability test (CAT), a visuo-spatial divergent thinking task, outside the scanner. Overall performances were comparable, although MPT performance indicated an advantage for adolescents in creative problem solving. In addition, adolescents showed more activation in lateral prefrontal cortex (ventral and dorsal) during creative problem solving compared to adults. These areas correlated with performances on the MPT and the CAT performance. We discuss that extended prefrontal cortex activation in adolescence is important for exploration and aids in creative cognition.     

The role of ventral medial prefrontal cortex in social decisions: Converging evidence from fMRI and frontotemporal lobar degeneration

The ventral medial prefrontal cortex (vmPFC) has been implicated in social and affectively influenced decision-making. Disease in this region may have clinical consequences for social judgments in patients with frontotemporal lobar degeneration (FTLD). To test this hypothesis, regional cortical activation was monitored with fMRI while healthy adults judged the acceptability of brief social scenarios such as cutting into a movie ticket line or going through a red light at 2 AM. The scenarios described: (i) a socially neutral condition, (ii) a variant of each scenario containing a negatively valenced feature, and (iii) a variant containing a positively valenced feature. Results revealed that healthy adults activated vmPFC during judgments of negatively valenced scenarios relative to positive scenarios and neutral scenarios. In a comparative behavioral study, the same social decision-making paradigm was administered to patients with a social disorder due to FTLD. Patients differed significantly from healthy controls, specifically showing less sensitivity to negatively valenced features. Comparative anatomical analysis revealed considerable overlap of vmPFC activation in healthy adults and vmPFC cortical atrophy in FTLD patients. These converging results support the role of vmPFC in social decision-making where potentially negative consequences must be considered.     

Prefrontal cortex activity is reduced in gambling and nongambling substance users during decision-making

OBJECTIVE: Poor decision-making is a hallmark of addiction, whether to substances or activities. Performance on a widely used test of decision-making, the Iowa Gambling Task (IGT), can discriminate controls from persons with ventral medial frontal lesions, substance-dependence, and pathological gambling. Positron emission tomography (PET) studies indicate that substance-dependent individuals show altered prefrontal activity on the task. Here we adapted the IGT to an fMRI setting to test the hypothesis that defects in ventral medial and prefrontal processing are associated with impaired decisions that involve risk but may differ depending on whether substance dependence is comorbid with gambling problems. METHOD: 18 controls, 14 substance-dependent individuals (SD), and 16 SD with gambling problems (SDPG) underwent fMRI while performing a modified version of the IGT. RESULT: Group differences were observed in ventral medial frontal, right frontopolar, and superior frontal cortex during decision-making. Controls showed the greatest activity, followed by SDPG, followed by SD. CONCLUSION: Our results support a hypothesis that defects in ventral medial frontal processing lead to impaired decisions that involve risk. Reductions in right prefrontal activity during decision-making appear to be modulated by the presence of gambling problems and may reflect impaired working memory, stimulus reward valuation, or cue reactivity in substance-dependent individuals.     

The neural basis of risk ratings: evidence from a functional magnetic resonance imaging (fMRI) study

Research investigating risk perception suggests that not only the quantitative parameters used in technical risk assessment (i.e., frequency and severity of harm) but also ‘qualitative’ aspects such as the dread a hazard provokes or its controllability influence risk judgments. It remains to be elucidated, however, which neural mechanism underlie risk ratings in healthy subjects. Using fMRI to detect changes in neural activity we compared the neural activations elicited by risk ratings with those elicited by a letter detection task performed on the same stimuli. The latter task served to control for basic stimulus processing, response selection and button-pressing during task performance. Risk ratings differentially activated the medial prefrontal cortex, the inferior frontal gyrus, the cerebellum (P < 0.05, FWE corrected, whole brain approach), and in an additional ROI analysis the amygdala (P < 0.05, FWE corrected). Of these structures, particularly the amygdala and the prefrontal cortex have been previously associated with decisions about affective interference. Furthermore our data suggest both, similarities and differences between the neural correlates of risk ratings and risk taking as involved, for e.g., in gambling tasks.     

Selective activation of the ventrolateral prefrontal cortex in the human brain during active retrieval processing

The present study examined the role of the prefrontal cortex in retrieval processing using functional magnetic resonance imaging in human subjects. Ten healthy subjects were scanned while they performed a task that required retrieval of specific aspects of visual information. In order to examine brain activity specifically associated with retrieval, we designed a task that had retrieval and control conditions that were perfectly matched in terms of depth of encoding, decision making and postretrieval monitoring and differed only in terms of whether retrieval was required. In the retrieval condition, based on an instructional cue, the subjects had to retrieve either the particular stimulus that was previously presented or its location. In the control condition, the cue did not instruct retrieval but shared with the instructional cues the function of alerting the subjects of the impending test phase. The comparison of activity between the retrieval and control conditions demonstrated a significant and selective increase in activity related to retrieval processes within the ventrolateral prefrontal cortical region, more specifically within area 47/12. These activity increases were bilateral but stronger in the right hemisphere. The present study by strictly controlling the level of encoding, postretrieval monitoring, and decision making has demonstrated a specific increase in the ventrolateral prefrontal region that could be clearly related to active retrieval processing, i.e. the active selection of particular stored visual representations.     

Predictions interact with missing sensory evidence in semantic processing areas

Human brain function draws on predictive mechanisms that exploit higher‐level context during lower‐level perception. These mechanisms are particularly relevant for situations in which sensory information is compromised or incomplete, as for example in natural speech where speech segments may be omitted due to sluggish articulation. Here, we investigate which brain areas support the processing of incomplete words that were predictable from semantic context, compared with incomplete words that were unpredictable. During functional magnetic resonance imaging (fMRI), participants heard sentences that orthogonally varied in predictability (semantically predictable vs. unpredictable) and completeness (complete vs. incomplete, i.e. missing their final consonant cluster). The effects of predictability and completeness interacted in heteromodal semantic processing areas, including left angular gyrus and left precuneus, where activity did not differ between complete and incomplete words when they were predictable. The same regions showed stronger activity for incomplete than for complete words when they were unpredictable. The interaction pattern suggests that for highly predictable words, the speech signal does not need to be complete for neural processing in semantic processing areas. Hum Brain Mapp 37:704–716, 2016. © 2015 Wiley Periodicals, Inc.     

Semantic processing in children with cochlear implants: Evidence from event-related potentials

Introduction: Existing research has shown that children with significant hearing loss who use cochlear implants (CIs) perform worse than their hearing peers on behavioral measures of spoken language. The present study sought to examine how children with CIs process lexical–semantic incongruence, as indexed by electrophysiological evidence of the N400 effect.

Method: Twelve children with CIs, aged between 6 and 9 years, participated in a spoken word–picture matching task while event-related potentials (ERPs) were recorded. To determine whether the N400 effect elicited in this group deviated from normal, independent samples t tests and analysis of variance (ANOVA) analyses were used to compare the results of children with CIs against those of a similarly aged typically hearing (TH) group (n = 30). Correlational analyses were also conducted within each group to gauge the degree to which the N400 effect related to behavioral measures of spoken language.

Results: An N400 effect was elicited in both groups of CI and TH children. The amplitude and latency of the N400 effect did not differ significantly between groups. Despite the similarity in ERP responses, children with CIs scored significantly lower on behavioral measures of spoken word- and sentence-level comprehension. No significant correlations between ERP and behavioral measures were found, although there was a trending relationship between sentence-level spoken language comprehension and the TH group’s N400 effect mean amplitude (p = .060).

Conclusions: The results suggest that, at a neural level, children with CIs can process lexical–semantic incongruence, and that other underlying processes not measured by the N400 effect contribute to this population’s spoken language difficulties.     

Recursion in action: An fMRI study on the generation of new hierarchical levels in motor sequences

Generation of hierarchical structures, such as the embedding of subordinate elements into larger structures, is a core feature of human cognition. Processing of hierarchies is thought to rely on lateral prefrontal cortex (PFC). However, the neural underpinnings supporting active generation of new hierarchical levels remain poorly understood. Here, we created a new motor paradigm to isolate this active generative process by means of fMRI. Participants planned and executed identical movement sequences by using different rules: a Recursive hierarchical embedding rule, generating new hierarchical levels; an Iterative rule linearly adding items to existing hierarchical levels, without generating new levels; and a Repetition condition tapping into short term memory, without a transformation rule. We found that planning involving generation of new hierarchical levels (Recursive condition vs. both Iterative and Repetition) activated a bilateral motor imagery network, including cortical and subcortical structures. No evidence was found for lateral PFC involvement in the generation of new hierarchical levels. Activity in basal ganglia persisted through execution of the motor sequences in the contrast Recursive versus Iteration, but also Repetition versus Iteration, suggesting a role of these structures in motor short term memory. These results showed that the motor network is involved in the generation of new hierarchical levels during motor sequence planning, while lateral PFC activity was neither robust nor specific. We hypothesize that lateral PFC might be important to parse hierarchical sequences in a multi‐domain fashion but not to generate new hierarchical levels.     

Automatic activation of the semantic network in schizophrenia: evidence from event-related brain potentials.

BACKGROUND: Language disorder associated with schizophrenia might be due to disturbances in both automatic activation and mechanisms of controlled attention. The contribution of each process to semantic memory dysfunction has not been determined for schizophrenia, and the semantic priming paradigm is well-suited for addressing this question. In the present report, event-related potentials (ERPs) elicited under conditions assumed to reveal automatic activation (short prime-target interval and low proportion of related words) are compared directly with ERPs elicited under conditions associated with controlled processing (long prime-target interval and high proportion of related words). METHODS: Visual ERPs were recorded during a lexical decision task, in which semantic relationship (associated and unassociated words), expectancy (relatedness proportions), and prime-target interval (250- and 850-msec inter-stimulus intervals [ISIs]) were varied. Diagnosis and expectancy were between-subjects factors; semantic relationship and ISI were repeated measures. The N400 priming effect (enhanced negativity to unassociated words) was compared between 34 male normal control subjects tested once and 37 male schizophrenia inpatients evaluated during their participation in a double-blind haloperidol maintenance therapy and placebo replacement protocol. RESULTS: The N400 priming effect for patients was significantly reduced during both pharmacologic phases, compared with controls. During haloperidol treatment, however, patients showed a significant N400 priming effect over the anterior scalp region and additionally under the automatic activation condition. The N400 priming effect was enhanced under the controlled processing condition for control subjects; this effect was not observed for patients. N400 amplitude elicited under the rapid presentation rate (250-msec ISI) differed between medicated patients and controls; groups did not differ for the 850-msec ISI. CONCLUSIONS: Findings suggest that automatic activation and mechanisms of controlled attention are both disrupted during semantic memory access for schizophrenia patients. Pharmacologic agents, such as haloperidol, might enhance automatic activation of the semantic network in this patient population, as indexed by the N400 component of the ERP.     

Reciprocal modulation and attenuation in the prefrontal cortex: an fMRI study on emotional-cognitive interaction

Everyday and clinical experience demonstrate strong interactions between emotions and cognitions. Nevertheless the neural correlates underlying emotional-cognitive interaction remain unclear. Using event-related fMRI, we investigated BOLD-signal increases and decreases in medial and lateral prefrontal cortical regions during emotional and non-emotional judgment of photographs taken from the International Affective Picture System (IAPS). Emotional and non-emotional judgment conditions were compared to each other as well as with baseline allowing for distinction between relative signal changes (comparison between conditions) and true signal changes (referring to baseline). We have found that: (1) both emotional and non-emotional judgment of IAPS pictures were characterized by signal increases in ventrally and dorsally located lateral prefrontal cortical areas and concurrent signal decreases in ventro- and dorsomedial prefrontal cortex; (2) direct comparison between emotional and non-emotional judgment showed relative signal increases in ventro- and dorsomedial prefrontal cortex, and in contrast, relative signal increases were detected in ventrally and dorsally located lateral prefrontal cortical areas when comparing non-emotional to emotional judgment; and (3) as shown in separate comparisons with baseline, these relative signal changes were due to smaller signal decreases in ventro- and dorsomedial prefrontal cortex and smaller signal increases in ventrally and dorsally located lateral prefrontal cortical areas during emotional judgment. Therefore, the emotional load of a cognitive task lead to both less deactivation of medial prefrontal regions and, at the same time, less activation of lateral prefrontal regions. Analogous patterns of reciprocal modulation and attenuation have previously been described for other cortical regions such as visual and auditory areas. Reciprocal modulation and attenuation in medial and lateral prefrontal cortex might constitute the neurophysiologic basis for emotional-cognitive interaction as observed in both healthy and psychiatric subjects.