Distributed neural system for general intelligence revealed by lesion mapping.

General intelligence (g) captures the performance variance shared across cognitive tasks and correlates with real-world success. Yet it remains debated whether g reflects the combined performance of brain systems involved in these tasks or draws on specialized systems mediating their interactions. Here we investigated the neural substrates of g in 241 patients with focal brain damage using voxel-based lesion-symptom mapping. A hierarchical factor analysis across multiple cognitive tasks was used to derive a robust measure of g. Statistically significant associations were found between g and damage to a remarkably circumscribed albeit distributed network in frontal and parietal cortex, critically including white matter association tracts and frontopolar cortex. We suggest that general intelligence draws on connections between regions that integrate verbal, visuospatial, working memory, and executive processes.

Deciding advantageously before knowing the advantageous strategy.

Deciding advantageously in a complex situation is thought to require overt reasoning on declarative knowledge, namely, on facts pertaining to premises, options for action, and outcomes of actions that embody the pertinent previous experience. An alternative possibility was investigated: that overt reasoning is preceded by a nonconscious biasing step that uses neural systems other than those that support declarative knowledge. Normal participants and patients with prefrontal damage and decision-making defects performed a gambling task in which behavioral, psychophysiological, and self-account measures were obtained in parallel. Normals began to choose advantageously before they realized which strategy worked best, whereas prefrontal patients continued to choose disadvantageously even after they knew the correct strategy. Moreover, normals began to generate anticipatory skin conductance responses (SCRs) whenever they pondered a choice that turned out to be risky, before they knew explicitly that it was a risky choice, whereas patients never developed anticipatory SCRs, although some eventually realized which choices were risky. The results suggest that, in normal individuals, nonconscious biases guide behavior before conscious knowledge does. Without the help of such biases, overt knowledge may be insufficient to ensure advantageous behavior.

Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans.

A patient with selective bilateral damage to the amygdala did not acquire conditioned autonomic responses to visual or auditory stimuli but did acquire the declarative facts about which visual or auditory stimuli were paired with the unconditioned stimulus. By contrast, a patient with selective bilateral damage to the hippocampus failed to acquire the facts but did acquire the conditioning. Finally, a patient with bilateral damage to both amygdala and hippocampal formation acquired neither the conditioning nor the facts. These findings demonstrate a double dissociation of conditioning and declarative knowledge relative to the human amygdala and hippocampus.

The return of Phineas Gage: clues about the brain from the skull of a famous patient.

When the landmark patient Phineas Gage died in 1861, no autopsy was performed, but his skull was later recovered. The brain lesion that caused the profound personality changes for which his case became famous has been presumed to have involved the left frontal region, but questions have been raised about the involvement of other regions and about the exact placement of the lesion within the vast frontal territory. Measurements from Gage's skull and modern neuroimaging techniques were used to reconstitute the accident and determine the probable location of the lesion. The damage involved both left and right prefrontal cortices in a pattern that, as confirmed by Gage's modern counterparts, causes a defect in rational decision making and the processing of emotion.

Differential effects of insular and ventromedial prefrontal cortex lesions on risky decision-making.

The ventromedial prefrontal cortex (vmPFC) and insular cortex are implicated in distributed neural circuitry that supports emotional decision-making. Previous studies of patients with vmPFC lesions have focused primarily on decision-making under uncertainty, when outcome probabilities are ambiguous (e.g. the Iowa Gambling Task). It remains unclear whether vmPFC is also necessary for decision-making under risk, when outcome probabilities are explicit. It is not known whether the effect of insular damage is analogous to the effect of vmPFC damage, or whether these regions contribute differentially to choice behaviour. Four groups of participants were compared on the Cambridge Gamble Task, a well-characterized measure of risky decision-making where outcome probabilities are presented explicitly, thus minimizing additional learning and working memory demands. Patients with focal, stable lesions to the vmPFC (n = 20) and the insular cortex (n = 13) were compared against healthy subjects (n = 41) and a group of lesion controls (n = 12) with damage predominantly affecting the dorsal and lateral frontal cortex. The vmPFC and insular cortex patients showed selective and distinctive disruptions of betting behaviour. VmPFC damage was associated with increased betting regardless of the odds of winning, consistent with a role of vmPFC in biasing healthy individuals towards conservative options under risk. In contrast, patients with insular cortex lesions failed to adjust their bets by the odds of winning, consistent with a role of the insular cortex in signalling the probability of aversive outcomes. The insular group attained a lower point score on the task and experienced more 'bankruptcies'. There were no group differences in probability judgement. These data confirm the necessary role of the vmPFC and insular regions in decision-making under risk. Poor decision-making in clinical populations can arise via multiple routes, with functionally dissociable effects of vmPFC and insular cortex damage.

Humans and great apes share a large frontal cortex.

Some of the outstanding cognitive capabilities of humans are commonly attributed to a disproportionate enlargement of the human frontal lobe during evolution. This claim is based primarily on comparisons between the brains of humans and of other primates, to the exclusion of most great apes. We compared the relative size of the frontal cortices in living specimens of several primate species, including all extant hominoids, using magnetic resonance imaging. Human frontal cortices were not disproportionately large in comparison to those of the great apes. We suggest that the special cognitive abilities attributed to a frontal advantage may be due to differences in individual cortical areas and to a richer interconnectivity, none of which required an increase in the overall relative size of the frontal lobe during hominid evolution.

Impairment of social and moral behavior related to early damage in human prefrontal cortex.

The long-term consequences of early prefrontal cortex lesions occurring before 16 months were investigated in two adults. As is the case when such damage occurs in adulthood, the two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities, and showed insensitivity to future consequences of decisions, defective autonomic responses to punishment contingencies and failure to respond to behavioral interventions. Unlike adult-onset patients, however, the two patients had defective social and moral reasoning, suggesting that the acquisition of complex social conventions and moral rules had been impaired. Thus early-onset prefrontal damage resulted in a syndrome resembling psychopathy.

Subcortical and cortical brain activity during the feeling of self-generated emotions.

In a series of [15O]PET experiments aimed at investigating the neural basis of emotion and feeling, 41 normal subjects recalled and re-experienced personal life episodes marked by sadness, happiness, anger or fear. We tested the hypothesis that the process of feeling emotions requires the participation of brain regions, such as the somatosensory cortices and the upper brainstem nuclei, that are involved in the mapping and/or regulation of internal organism states. Such areas were indeed engaged, underscoring the close relationship between emotion and homeostasis. The findings also lend support to the idea that the subjective process of feeling emotions is partly grounded in dynamic neural maps, which represent several aspects of the organism's continuously changing internal state.

Single-neuron responses to emotional visual stimuli recorded in human ventral prefrontal cortex.

Both lesion and functional imaging studies in humans, as well as neurophysiological studies in nonhuman primates, demonstrate the importance of the prefrontal cortex in representing the emotional value of sensory stimuli. Here we investigated single-neuron responses to emotional stimuli in an awake person with normal intellect. Recording from neurons within healthy tissue in ventral sites of the right prefrontal cortex, we found short-latency (120-160 ms) responses selective for aversive visual stimuli.

The Iowa Gambling Task and the somatic marker hypothesis: some questions and answers.

A recent study by Maia and McClelland on participants' knowledge in the Iowa Gambling Task suggests a different interpretation for an experiment we reported in 1997. The authors use their results to question the evidence for the somatic marker hypothesis. Here we consider whether the authors' conclusions are justified.

A role for somatosensory cortices in the visual recognition of emotion as revealed by three-dimensional lesion mapping.

Although lesion and functional imaging studies have broadly implicated the right hemisphere in the recognition of emotion, neither the underlying processes nor the precise anatomical correlates are well understood. We addressed these two issues in a quantitative study of 108 subjects with focal brain lesions, using three different tasks that assessed the recognition and naming of six basic emotions from facial expressions. Lesions were analyzed as a function of task performance by coregistration in a common brain space, and statistical analyses of their joint volumetric density revealed specific regions in which damage was significantly associated with impairment. We show that recognizing emotions from visually presented facial expressions requires right somatosensory-related cortices. The findings are consistent with the idea that we recognize another individual's emotional state by internally generating somatosensory representations that simulate how the other individual would feel when displaying a certain facial expression. Follow-up experiments revealed that conceptual knowledge and knowledge of the name of the emotion draw on neuroanatomically separable systems. Right somatosensory-related cortices thus constitute an additional critical component that functions together with structures such as the amygdala and right visual cortices in retrieving socially relevant information from faces.

Auditory cortex on the human posterior superior temporal gyrus.

The human superior temporal cortex plays a critical role in hearing, speech, and language, yet its functional organization is poorly understood. Evoked potentials (EPs) to auditory click-train stimulation presented binaurally were recorded chronically from penetrating electrodes implanted in Heschl's gyrus (HG), from pial-surface electrodes placed on the lateral superior temporal gyrus (STG), or from both simultaneously, in awake humans undergoing surgery for medically intractable epilepsy. The distribution of averaged EPs was restricted to a relatively small area on the lateral surface of the posterior STG. In several cases, there were multiple foci of high amplitude EPs lying along this acoustically active portion of STG. EPs recorded simultaneously from HG and STG differed in their sensitivities to general anesthesia and to changes in rate of stimulus presentation. Results indicate that the acoustically active region on the STG is a separate auditory area, functionally distinct from the HG auditory field(s). We refer to this acoustically sensitive area of the STG as the posterior lateral superior temporal area (PLST). Electrical stimulation of HG resulted in short-latency EPs in an area that overlaps PLST, indicating that PLST receives a corticocortical input, either directly or indirectly, from HG. These physiological findings are in accord with anatomic evidence in humans and in nonhuman primates that the superior temporal cortex contains multiple interconnected auditory areas.

A computed tomographic guide to the identification of cerebral vascular territories.

This article presents a system of human brain templates, depicting territories of cerebrovascular supply and cortical cytoarchitectonic markings. The templates may be used as a guide to localization of abnormal images in standard computed tomographic cuts.

Three-dimensional in vivo mapping of brain lesions in humans.

We describe a multistep technique for three-dimensional reconstruction and analysis of brain lesions in vivo, based on the manipulation of magnetic resonance raw data obtained with a special protocol. The technique permits the direct visual identification of neuroanatomical landmarks in each brain specimen and eliminates the need to rely on averaged templates of human brain sections, which can be a source of lesion localization error. The technique also allows for the bidirectional cross-reference between data points in two-dimensional slices and in volume reconstruction and for the projection of subcortical structures onto the three-dimensional cortical surface. The three-dimensional lesion mapping technique can be applied to research with the lesion method in both human and nonhuman primates, to the planning of neurosurgical lesion approach, and to the teaching of neuroanatomy.

Neuropsychological impairments associated with lesions caused by tumor or stroke.

Populations of patients with strokes or tumors constitute the most frequently used subjects in neuropsychological research, and these populations are often combined when the investigation aims at establishing brain-behavior relationships. We compared these two populations with respect to their neuropsychological profiles. Seventeen subjects with tumors were individually matched to subjects with unilateral strokes on the basis of lesion location. Despite close matching of lesions, there were major differences in the neuropsychological impairments of the two groups, eg, all subjects with stroke in the left hemisphere had more severe language defects than did their counterparts with tumors, and some tumor subjects performed normally on all neuropsychological tests. These findings demonstrate that the cognitive and/or behavioral consequences of tumors or strokes in similar locations can be radically different. The two patient types should be treated separately for the purpose of neuropsychological research.

Computerized tomographic scan findings in patients with autistic behavior.

An analysis of the computerized tomography scans of 17 patients with autistic behavior was carried out by investigators independent from those selecting the subjects. Mild abnormalities of the ventricular system were noted in several scans (increased size, altered left/right relation of lateral ventricles), and in three scans major hydrocephalus and circumscribed lesions of the parenchyma were seen. It was not possible to discern a singular abnormal pattern, the abnormalities appearing consequent to a variety of disease processes of the CNS.

Aphasia with nonhemorrhagic lesions in the basal ganglia and internal capsule.

Atypical aphasia syndromes were associated with circumscribed nonhemorrhagic infarctions of the anterior limb of the internal capsule and of the striatum, in the dominant hemisphere. None of the several cases could be classified in terms of the classic cortical aphasia syndromes, nor did they correspond to the description of aphasia produced by hemorrhage in the thalamus or putamen. Control subjects without aphasia had lesions in the same structures of the nondominant hemisphere, or they had comparably circumscribed damage, which was located lateral or caudal to the previously indicated locus. The findings raise the question of participation of the dominant striatum, and of the connectional systems that course in the anterior limb of the internal capsule, in language processing.

Transient partial amnesia.

A patient struck with transient amnesia was able to write a detailed account of her experiences during the episode and retained partial memory of the event. The analysis of her report permits an unusual view of transient partial amnesia.

Developmental consequences of childhood frontal lobe damage.

A 33-year-old woman underwent neurologic and neuropsychological studies 26 years after she sustained damage to the frontal lobe. The findings of the neurologic examination were normal, and magnetic resonance imaging revealed a lesion in left prefrontal cortex and deep white matter. Cerebral blood flow studies showed an abnormal pattern in both left and right frontal regions. The patient exhibited striking neuropsychological defects in higher cognition, most notably in self-regulation of emotion and affect and in social behavior. Analysis of her behavioral development failed to yield a pattern of abrupt onset of defect immediately after the lesion occurred. On the contrary, there was a delayed onset of defects, followed by a period of seeming progression, and finally an arrest of development in adolescence. We suggest that this peculiar pattern is the natural consequence of the varied changes that occurred in brain development and social cognition during the patient's formative years. While certain long-term neuropsychological deficits in our case are similar to those following frontal damage in adults, the delayed onset and progression of deficits are different.

Multiple cerebral aneurysms and cardiac myxoma.

Neurological signs are a frequent manifestation of left atrial myxoma, but the association of cardiac myxoma with multiple cerebral aneurysms is rare. A case of left atrial myxoma was detected in the course of a long-lasting psychiatric and neurological illness. Four-vessel study showed the presence of multiple saccular and fusiform aneurysms, regularly and almost symmetrically distributed. The intracardiac mass was removed, and the patient improved.