Knowledge without awareness: an autonomic index of facial recognition by prosopagnosics.

Prosopagnosia, the inability to recognize visually the faces of familiar persons who continue to be normally recognized through other sensory channels, is caused by bilateral cerebral lesions involving the visual system. Two patients with prosopagnosia generated frequent and large electrodermal skin conductance responses to faces of persons they had previously known but were now unable to recognize. They did not generate such responses to unfamiliar faces. The results suggest that an early step of the physiological process of recognition is still taking place in these patients, without their awareness but with an autonomic index.

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.

Alzheimer's disease: cell-specific pathology isolates the hippocampal formation.

Examination of temporal lobe structures from Alzheimer patients reveals a specific cellular pattern of pathology of the subiculum of the hippocampal formation and layers II and IV of the entorhinal cortex. The affected cells are precisely those that interconnect the hippocampal formation with the association cortices, basal forebrain, thalamus, and hypothalamus, structures crucial to memory. This focal pattern of pathology isolates the hippocampal formation from much of its input and output and probably contributes to the memory disorder in Alzheimer patients.

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.

Category-related recognition defects as a clue to the neural substrates of knowledge.

Circumscribed damage to human cerebral cortex can lead to a surprisingly selective breakdown of recognition. Patients may be unable to recognize a person's identity from their face, but retain the ability to recognize identity from gait, or they may experience a disproportionate difficulty in recognizing entities belonging to certain conceptual categories, such as natural kinds, and no difficulty in recognizing man-made items. The relation between such patterns of breakdown and the underlying damage to specific cortical regions suggests a possible organization for the neural substrates of knowledge, at the level of systems. In general, it appears that different neural systems are dedicated to the processing of certain characteristics of entities and events, in certain knowledge domains, but that systems are not dedicated to the representation of particular conceptual categories.

Knowledge systems.

The primate brain appears to store knowledge in widely distributed neural systems. Recent evidence suggests that these systems are specialized with respect to their capacity for supporting acquisition and retrieval of different domains and levels of knowledge.

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.

Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia.

The cytoarchitecture of the entorhinal cortex was examined in the brains of six patients with a diagnosis of schizophrenia and in 16 controls. All six brains of schizophrenic patients showed abnormalities of the rostral and intermediate portions of the entorhinal cortex. The abnormalities included aberrant invaginations of the surface, disruption of cortical layers, heterotopic displacement of neurons, and paucity of neurons in superficial layers. These changes suggest disturbed development. Because the entorhinal cortex is pivotal for neural systems that mediate corticohippocampal interactions, early disruption of its structure could lead to important neuropsychological changes during development and in adult life and could contribute to the symptomatology of schizophrenia.

Hemispheric asymmetries and schizophrenia.

Investigators have hypothesized that schizophrenic patients have abnormal left hemisphere function or deviations from normal function asymmetry. It has also been suggested that schizophrenic patients have reversal of normal structural asymmetries. The authors measured frontal and occipital petalia and frontal and occipital width of each hemisphere on the CT scans of 43 right-handed schizophrenic patients and 40 right-handed control subjects. There were no significant differences in structural asymmetry between the groups. The 8 left-handed schizophrenic patients may have had abnormal functional asymmetries; their mean ventricular-brain ratio, a possible indirect indicator of cerebral atrophy, was higher than that of the right-handed patients.

A neurological model for childhood autism.

We analyze the behavioral and motor disturbances in childhood autism. On the basis of analogy to signs and conditions seen in adult neurology, we propose that the syndrome results from dysfunction in a system of bilateral neural structures that includes the ring of mesolimbic cortex located in the mesial frontal and temporal lobes, the neostriatum, and the anterior and medial nuclear groups of the thalamus. The mesolimbic cortex is cytoarchitectonically, angioarchitectonically, and neurochemically distinct and, along with the striatum, forms the entire target area of dopaminergic mesencephalic neurons. This raises the possibility that autism is related to neuromediator imbalance in those structures. Such dysfunction might be the result of macroscopic or microscopic changes in the target area or in structures functionally influencing them, consequent to a variety of causes such as perinatal viral infection, insult to the periventricular watershed area, or genetically determined neurochemical abnormalities.

Praxis and writing of the left hand may be served by different callosal pathways.

A patient who had damage to the leftward outflow of the body of the corpus callosum experienced the development of agraphia, but not apraxia, of the left hand. In another case reported recently, a similar lesion produced the same intriguing dissociation. We suggest that the principal interhemispheric controls for praxis and for writing of the left hand operate at different levels of the corpus callosum.

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.

Gait disturbances in patients with autistic behavior: a preliminary study.

Kinesiologic analysis of the gaits of 21 autistic, 15 normal, and five hyperactive-aggressive children revealed that the autistic patients had (a) reduced stride lengths, (b) increased stance times, (c) increased hip flexion at "toe-off," and (d) decreased knee extension and ankle dorsiflexion at ground contact. In many respects, the gait differences between the autistic and normal subjects resembled differences between the gaits of parkinsonian patients and of normal adults. These preliminary results are compatible with the view that the autistic syndrome may be associated with specific dysfunction of the motor system affecting, among other structures, the basal ganglia.

Aphasia following pluridirectional tomography with metrizamide. The effect of patient position.

Eight of 67 patients became transiently aphasic after myelography or cisternography with metrizamide. All eight patients had been placed in the left lateral decubitus position for pluridirectional tomography. Immediate EEGs revealed focal left-sided abnormalities in two patients. In one other patient, a computed tomographic scan showed contrast mainly over the left hemisphere. All of the symptoms resolved within 48 hours. In 34 patients who were placed on the right side, no language disturbance was noted. Aphasia after pluridirectional tomography with metrizamide may be due to local irritation of the perisylvian language centers of the dominant hemisphere. The phenomenon is distinct from syndromes of generalized confusion. The complication may be avoided by placing patients in a right lateral decubitus position for pluridirectional tomography.

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.