Phineas gauged: decision-making and the human prefrontal cortex

Poor social judgment and decision-making abilities have often been attributed to people who have suffered injury to the ventromedial prefrontal cortex (VMPFC). However, few laboratory tests of decision-making have been conducted on these patients. The exception to this is the Iowa Gambling Task which has often, but not always, demonstrated differential performance between patients and controls. Results from patients with prefrontal cortex lesions on a novel test of decision-making are presented. Participants explored and chose from pairs of gambles that differed in their underlying distributions, primarily in the variance of their respective outcomes. In accordance with many findings from the behavioral decision-making literature, both young normal participants and older patient controls demonstrated a marked avoidance of risk and selected largely from secure, low variance gambles. In contrast, patients with ventromedial lesions were divided into two clear sub-groups. One group behaved similarly to normals, showing a risk-averse strategy. The other group displayed a distinctive risk-seeking behavior pattern, choosing predominantly from the high-variance, high-risk decks. This research demonstrates some of the advantages of using methods and theories from traditional decision-making research to study the behavior of patients, as well as the benefits of examining individual participants, and provides new insights into the nature of the decision-making deficit in patients with ventromedial prefrontal cortex lesions.     

When Broca experiences the Janus syndrome: an ER-fMRI study comparing sentence comprehension and cognitive sequence processing

The determining of brain regions that exhibit specific activity during sentence comprehension compared to other non-linguistic cognitive tasks constitutes one of the important challenges in the domain of functional neuroimaging of the faculty of language. In the current paper we report an event-related functional magnetic resonance imaging (ER-fMRI) experiment, in which we directly compared the cerebral basis of sentence comprehension on the one hand, and of abstract sequence processing on the other hand. Previous experimental work done in our group, as well as different observations from recent behavioural, neurophysiological and functional neuroimaging experiments led us to propose the hypothesis that both of these tasks would share certain computational properties. Thus, this experiment was designed to show which brain regions would be implicated in both tasks and compare them to brain regions that would be specifically engaged in sentence comprehension. Results from this experiment suggest that distinct sub-regions in the left prefrontal cortex, potentially including Broca's area show distinct activation patterns during both of these tasks. Results are discussed in the context of a construction-based model of sentence processing (see Dominey and Hoen, 2006, this issue) that is based on a dual-path processing mechanism separating function and content information processing. We propose and discuss the hypothesis that subparts of Broca's area BA 44 and BA 45 would respectively be implicated in two different aspects of sentence comprehension: i) a general structure mapping capability and ii) the online integration of semantic representations onto structural constraints.     

Unification of sentence processing via ear and eye: An fMRI study

We present new evidence based on fMRI for the existence and neural architecture of an abstract supramodal language system that can integrate linguistic inputs arising from different modalities such that speech and print each activate a common code. Working with sentence material, our aim was to find out where the putative supramodal system is located and how it responds to comprehension challenges. To probe these questions we examined BOLD activity in experienced readers while they performed a semantic categorization task with matched written or spoken sentences that were either well-formed or contained anomalies of syntactic form or pragmatic content. On whole-brain scans, both anomalies increased net activity over non-anomalous baseline sentences, chiefly at left frontal and temporal regions of heteromodal cortex. The anomaly-sensitive sites correspond approximately to those that previous studies ( [Constable et?al., 2004] and [Michael et?al., 2001] ) have found to be sensitive to other differences in sentence complexity (object relative minus subject relative). Regions of interest (ROIs) were defined by peak response to anomaly averaging over modality conditions. Each anomaly-sensitive ROI showed the same pattern of response across sentence types in each modality. Voxel-by-voxel exploration over the whole brain based on a cosine similarity measure of common function confirmed the specificity of supramodal zones.     

Conflict and cognitive control during sentence comprehension: recruitment of a frontal network during the processing of Spanish object-first sentences

During sentence processing there is a preference to treat the first noun phrase found as the subject and agent, unless marked the other way. This preference would lead to a conflict in thematic role assignment when the syntactic structure conforms to a non-canonical object-before-subject pattern. Left perisylvian and fronto-parietal brain networks have been found to be engaged by increased computational demands during sentence comprehension, while event-reated brain potentials have been used to study the on-line manifestation of these demands. However, evidence regarding the spatiotemporal organization of brain networks in this domain is scarce. In the current study we used Magnetoencephalography to track spatio-temporally brain activity while Spanish speakers were reading subject- and object-first cleft sentences. Both kinds of sentences remained ambiguous between a subject-first or an object-first interpretation up to the appearance of the second argument. Results show the time-modulation of a frontal network at the disambiguation point of object-first sentences. Moreover, the time windows where these effects took place have been previously related to thematic role integration (300-500 ms) and to sentence reanalysis and resolution of conflicts during processing (beyond 500 ms post-stimulus). These results point to frontal cognitive control as a putative key mechanism which may operate when a revision of the sentence structure and meaning is necessary.     

The dynamic approach to neurodevelopmental psychiatric disorders: use of fMRI combined with neuropsychology to elucidate the dynamics of psychiatric disorders, exemplified in ADHD and schizophrenia

The paper discusses the application of fMRI in combination with neuropsychology to neurodevelopmental psychiatric disorders, exemplified on the case of attention deficit hyperactivity disorder (ADHD) in comparison with schizophrenia. The view is presented that ADHD, rather than being a compound of unrelated co-existing deficits, is a pervasive disorder of impulsiveness, which manifests at the motor, emotional, social and cognitive domain. Neuropsychology needs to refine the psychological measurements of these impulsivity symptoms and, in combination with fMRI, provide new insights into the interrelationship between brain and dysfunction and its bi-directional causalities. The suitability of the dynamic technique of functional MRI to assess the dynamic nature of developmental neuropsychiatric disorders is discussed. Brain activation can inform about strategy and compensatory mechanisms at a neuroanatomical level, which are not observable at a psychological level, providing insight into the underlying neurocognitive mechanisms of psychiatric disorders. Data are presented and discussed on opposing neurocognitive activation patterns for patients with ADHD and those with schizophrenia while performing a stop task. Comparisons between patient groups will be essential to address the specificity of neurocognitive mechanisms corresponding to specific neurodevelopmental psychiatric disorders.     

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.     

Response inhibition and impulsivity: an fMRI study

Aggressive, suicidal and violent behaviour have been associated with impulsive personality and difficulty in inhibiting responses. We used functional magnetic resonance imaging (fMRI) of the whole brain to examine the neural correlates of response inhibition in 19 normal subjects as they performed a Go/NoGo task. Subjects completed Eysenck’s Impulsivity Scale, Barratt’s Impulsivity Scale (BIS) and behavioural impulsivity tasks. Associations between blood oxygen level dependent (BOLD) response, trait impulsivity, task performance and National Adult Reading Test (NART) IQ were investigated. Neural response during response inhibition was most prominent in the right lateral orbitofrontal cortex. Responses were also seen in superior temporal gyrus, medial orbitofrontal cortex, cingulate gyrus, and inferior parietal lobule, predominantly on the right side. Subjects with greater scores on impulsivity scales and who made more errors had greater activation of paralimbic areas during response inhibition, while less impulsive individuals and those with least errors activated higher order association areas. Exploratory factor analysis of orbital activations, personality measures and errors of commission did not reveal a unitary dimension of impulsivity. However, the strong association between posterior orbital activation and Eysenck’s impulsivity score on a single factor suggests that greater engagement of right orbitofrontal cortex was needed to maintain behavioural inhibition in impulsive individuals. Lower IQ was more important than impulsivity scores in determining errors of commission during the task. Neuroimaging of brain activity during the Go/NoGo task may be useful in understanding the functional neuroanatomy and associated neurochemistry of response inhibition. It may also allow study of the effects of physical and psychological interventions on response inhibition in clinical conditions such as antisocial personality disorder.     

The role of the prefrontal cortex in sentence comprehension: an rTMS study

Using repetitive transcranial magnetic stimulation (rTMS), we investigated the role of the left and right dorsolateral prefrontal cortex (DLPFC) in sentence comprehension. Subjects were required to judge which of the two pictures correctly matched the meaning of active and passive semantically reversible sentences (subject-verb-object); the incorrect picture did not match the sentence in term of lexical items (semantic task) or agent-patient structure (syntactic task). The subjects performed the task while a series of magnetic stimuli were applied to the left or right DLPFC. When rTMS was applied to the left DLPFC, the subjects' performance was delayed only for the semantic task, while rTMS applied to the right DLPFC slowed the processing of syntactic information. The results of this experiment provide direct evidence of a double dissociation between the rTMS effects and the type of task, which may reflect a differential hemispheric involvement of working memory resources during sentence comprehension.     

Altered prefrontal brain activity in persons at risk for Alzheimer's disease: an fMRI study

BACKGROUND: Early diagnosis of Alzheimer's disease (AD) is critical for adequate treatment and care. Recently it has been shown that functional magnetic resonance imaging (fMRI) can be important in preclinical detection of AD. The purpose of this study was to examine possible differences in memory-related brain activation between persons with high versus low risk for AD. This was achieved by combining a validated neurocognitive screening battery (the 7-minutes test) with memory assessment and fMRI. METHODS: One hundred two healthy community-living persons with subjective memory complaints were recruited through advertisement and tested with the 7-minutes test. Based on their test performance they were classified as having either high (n = 8) or low risk (n = 94) for AD. Six high-risk individuals and six age-, sex-, and education-matched low-risk individuals were investigated with fMRI while engaged in episodic memory tasks. RESULTS: The high-risk individuals performed worse than low-risk individuals on tests of episodic memory. Patterns of brain activity during episodic encoding and retrieval showed significant group differences (p < .05 corrected). During both encoding and retrieval, the low-risk persons showed increased activity relative to a baseline condition in prefrontal brain regions that previously have been implicated in episodic memory. By contrast, the high-risk persons did not significantly activate any prefrontal regions, but instead showed increased activity in visual occipito-temporal regions. CONCLUSION: Patterns of prefrontal brain activity related to episodic memory differ between persons with high versus low risk for AD, and lowered prefrontal activity may predict subsequent disease.     

Memory consolidation and the hippocampus: further evidence from studies of autobiographical memory in semantic dementia and frontal variant frontotemporal dementia.

Studies of autobiographical memory in semantic dementia have found relative preservation of memories for recent rather than remote events. As semantic dementia is associated with progressive atrophy to temporal neocortex, with early asymmetric sparing of the hippocampus, this neuropsychological pattern suggests that the hippocampal complex plays a role in the acquisition and retrieval of recent memories, but is not necessary for the recall of older episodic events. In an alternative view of memory consolidation, however, the hippocampus plays a role in the retrieval of all autobiographical memories, regardless of the age of the memory [Curr. Opin. Neurobiol. 7(1997)217]. This 'multiple trace theory' predicts that patients with semantic dementia should show no effects of time in their autobiographical recall. In this article, we ask whether it is possible to reconcile the data from semantic dementia with the multiple trace theory by investigating whether the time-dependent pattern of autobiographical retrieval seen in the disease is due to (i) patients showing this effect being exceptional in their presentation; and/or (ii) patients with semantic dementia exhibiting impaired strategic retrieval from concomitant frontal damage. A series of experiments in patients with semantic dementia, the frontal variant of frontotemporal dementia and Alzheimer's disease clearly demonstrates that neither of these two factors can explain the documented effect of time seen in semantic dementia. Nonetheless, we discuss how damage to semantic knowledge could result in an autobiographical memory deficit and suggest that data from semantic dementia may be consistent with both views of hippocampal involvement in long-term memory.     

Enhanced amygdala and medial prefrontal activation during nonconscious processing of fear in posttraumatic stress disorder: an fMRI study

Biological models of posttraumatic stress disorder (PTSD) suggest that patients will display heightened amygdala but decreased medial prefrontal activity during processing of fear stimuli. However, a rapid and automatic alerting mechanism for responding to nonconscious signals of fear suggests that PTSD may display heightened rather than decreased MPFC under nonconscious processing of fear stimuli. This study used functional magnetic resonance imaging to examine blood oxygenation level-dependent signal changes during nonconscious presentation (16.7 ms, masked) of fearful and neutral faces in 15 participants with PTSD and 15 age and sex-matched healthy control participants. Results indicate that PTSD participants display increased amygdala and MPFC activity during nonconscious processing of fearful faces. These data extend existing models by suggesting that the impaired MPFC activation in PTSD may be limited to conscious fear processing. Hum Brain Mapp, 2008. (c) 2007 Wiley-Liss, Inc.     

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.     

Competition for priority in processing increases prefrontal cortex's involvement in top-down control: an event-related fMRI study of the stroop task

Prior work indicates that various aspects of task-irrelevant information (e.g. its salience, task-relatedness, emotionality) can increase the involvement of prefrontal cortex (PFC) in top-down attentional control. In light of these findings, we hypothesize that PFC's involvement increases when task-irrelevant information competes for priority in processing. In an event-related fMRI study using an oddball variant of the Stroop task, we examine the generality of this hypothesis using three manipulations designed to increase the ability of task-irrelevant information to compete for priority in processing. First, we investigated how the frequency of occurrence of task-irrelevant information affects PFC activity. Second, we examined whether conflicting color information (i.e. incongruent trials) increases activity in regions of PFC that are similar to or distinct from those sensitive to infrequently occurring task-irrelevant information. Finally, we examined the impact of the number of levels at which conflict could occur (e.g. non-response only, non-response and response). Activity in posterior-dorsolateral and posterior-inferior PFC increased for infrequently occurring task-irrelevant information, being largest when the task-irrelevant information contained conflicting color-information. In contrast, increases in mid-dorsolateral prefrontal cortex's activity were only noted when conflicting color information was present, being largest when conflict occurred at multiple levels. The anterior cingulate was primarily sensitive to the occurrence of conflict at the response level with only a small sub-region exhibiting sensitivity to non-response conflict as well. From these findings we suggest that posterior DLPFC and PIPFC are involved in biasing processing in posterior processing systems, mid-DLPFC is involved in biasing the processing of the contents of working memory, and ACC is primarily involved in response-related processes.     

Individual inconsistency across measures of inhibition: an investigation of the construct validity of inhibition in older adults.

Inhibition is a central construct to the frontal lobe theory of ageing, yet its construct validity remains unproven. Furthermore, age effects on measures of inhibition are often reported without adequate control for the effects of global slowing on performance. We investigated inhibitory function in older adults in two experiments. In Experiment 1, 49 people with ages between 59 and 86 (mean=70 years 9 months S.D.=7.54) completed four analogues of the Stroop interference paradigm. To control for global slowing and to enable comparisons across all measures, we used a random effects model based on log-transformed response times. Age did not contribute significantly to the model and the estimated correlation between tasks was not significant. In Experiment 2, 33 people with ages between 62 and 86 (mean=73 years 4 months, S.D.=6.57) were compared on two measures of Stroop-like interference which were very similar in surface task demands. Age did not contribute significantly to the model but the estimated correlation between tasks was robust (r=0.714). We conclude that age may make little contribution to inhibitory function independently of other factors such as speed and intelligence. Second, that the level of individual consistency in the performance of measures of inhibition will depend on the similarity of the tasks used.     

The prefrontal cortex and conscious monitoring of action: an experimental study

To investigate the role of the prefrontal cortex in conscious monitoring, we used an experimental paradigm generating a conflict between the action planned and the sensory-motor feedback. We analyzed the acquisition of explicit knowledge of the strategy for resolving the conflict and its influence on motor adaptation. Twenty patients with frontal lobe lesions and 18 controls had to trace a sagittal line with a stylus on a graphics tablet. A mirror on which the traced line, processed by a computer, was projected hid the hand. A mask limited visual feedback to the last third of the trajectory. Without informing the subjects, the line traced was modified by introducing a bias of 24 degrees to the right. To succeed in the task, subjects had to modify their motor program and to deviate their trajectory in the opposite direction. Conscious elaboration of the strategy was evaluated by the number of trials needed to explicitly report the required deviation. Three groups of patients were distinguished: (1). with normal explicit strategy; (2). with delayed explicit strategy, and (3). without explicit strategy at the last trial. They significantly differed by the severity of the dysexecutive syndrome, particularly of environmental adherence. Motor adaptation was evaluated by the area between the line traced and the ideal line to compensate for the deviation. In patients with normal elaboration of the strategy, motor control was similar to that of controls, but it was severely disturbed in the other two groups. These results suggest the involvement of the prefrontal cortex in conscious motor monitoring.     

Action representation in the superior temporal sulcus in children and adults: An fMRI study

The superior temporal sulcus (STS) plays an important role in the perception of biological motion and in the representation of higher order information about other's goals and intentions. Using a rapid event related functional magnetic resonance imaging paradigm (fMRI), children (n=37, mean age 11.0) and adults (n=17, mean age 25.3) viewed congruent or incongruent actions. Congruency (and incongruency) of a reach toward an object was a function of whether the object had just previously received positive or negative regard. Relative to congruent trials, both children and adults showed an increase in activation in the posterior STS bilaterally, in response to incongruent trials. In children, these STS regions exhibited developmental changes. Specifically, the differential response to incongruent trials relative to congruent trials was larger in older children in both hemispheres.     

Cortical mechanisms involved in the processing of verbs: an fMRI study

In this study, we investigated two aspects of verb processing: first, whether verbs are processed differently from nouns; and second, how verbal morphology is processed. For this purpose, we used functional magnetic resonance imaging to compare three types of lexical processing in Japanese: the processing of nouns, unmarked active verbs, and inflected passive verbs. Twenty-eight healthy subjects were shown a lexical item and asked to judge whether the presented item was a legal word. Although all three conditions activated the bilateral inferior frontal, occipital, the left middle, and inferior temporal cortices, we found differences in the degree of activation for each condition. Verbs elicited greater activation in the left middle temporal gyrus than nouns, and inflected verbs showed greater activation in the left inferior frontal gyrus than unmarked verbs. This study demonstrates that although verbs are basically processed in the same cortical network as nouns, nouns and verbs elicit different degrees of activation due to the cognitive demands involved in lexical semantic processing. Furthermore, this study also shows that the left inferior frontal cortex is related to the processing of verbal inflectional morphology.     

Beyond localization: the role of traditional neuropsychological tests in an age of imaging

Rapid advances in structural and functional magnetic resonance imaging (MRI) present two significant challenges to the rationale and role of the traditional neuropsychological assessment in the presurgical evaluation of epilepsy surgery candidates today. The first is a direct challenge to the model of material-specific memory that has underpinned much clinical practice over the last 50 years. The second, more fundamental, challenge goes to the very heart of the lateralizing/localizing approach that has been the cornerstone of clinical neuropsychology practice in epilepsy surgery centers to date. This review examines these challenges and suggests some ways in which the profession might respond and adapt. We conclude that noninvasive neuropsychological assessment remains a critical investigation in the presurgical evaluation of epilepsy surgery patients. Its value stretches beyond the localization of a surgically remediable seizure focus. Once a vital test, other investigations are now superior in this respect in many cases. However, new technologies have enhanced the role of the traditional neuropsychological assessment, which is now able to provide unparalleled insights and predictions into the way in which the underlying pathology, seizures, and proposed surgery shape an individual's profile of cognitive abilities. Detailed neuropsychological feedback enables the patient to make an informed decision, and forms the basis of the tailor made preemptive rehabilitation programs that can be implemented preoperatively, minimizing the most significant morbidity associated with epilepsy surgery today.