Paul J. Eslinger

Severe disturbance of higher cognition after bilateral frontal lobe ablation Patient EVR

After bilateral ablation of orbital and lower mesial frontal cortices, a patient had profound changes of behavior that have remained stable for 8 years. Although he could not meet personal and professional responsibilities, his “measurable” intelligence was superior, and he was therefore considered a “malingerer.” Neurologic and neuropsychological examinations were otherwise intact. CT, MRI, and SPET revealed a localized lesion of the orbital and lower mesial frontal cortices. All other cerebral areas had normal structure and radioactivity patterns. Such impairments of motivation and complex social behavior were not seen in control cases with superior mesial or dorsolateral frontal lesions.

Frontal lobe and frontal-striatal substrates for different forms of human cognitive flexibility.

Frontal lobe and basal ganglia lesions have been associated with similar cognitive impairments, although their specialized roles in behavior are likely to be different. We examined whether these structures mediate distinctive or overlapping aspects of a complex behavioral process that has been associated with both neural sites, i.e. cognitive flexibility. Patients with focal ischemic lesions to the frontal lobe and basal ganglia were compared on two forms of cognitive flexibility: (1) shifting response set (i.e. reactive flexibility), and (2) producing a diversity of ideas (i.e. spontaneous flexibility). Results indicated that frontal lobe and basal ganglia damage each caused a similar degree of impairment in reactive flexibility, both groups performing at a significantly lower level than posterior cortical lesion and normal comparison groups. However, frontal lobe damage markedly disturbed spontaneous flexibility, while performance after basal ganglia lesion was significantly higher and comparable to posterior cortical lesions. Findings suggest that the frontal lobe and basal ganglia participate differently in the neural substrate of cognitive flexibility. The frontal lobe appears to mediate spontaneous flexibility. The production of diverse ideas may require direct cortical-cortical interactions by the frontal lobe in order to access knowledge systems with novel strategies that transcend the most common semantic linkages. In contrast the corticostriate system appears to mediate reactive flexibility, as the frontal lobe, basal ganglia and their interconnections are required for its operation.

Neurological and neuropsychological bases of empathy

Impairments of social behavior after cerebral damage are often problematic and difficult to assess and manage, with few models addressing evaluation, treatment options and prognosis. Recent studies suggest that a fundamental mechanism of social behavior disturbed by acquired cerebral damage is empathy. Empathy refers to the cognitive and emotional processes that bind people together in various kinds of relationships that permit sharing of experiences as well as understanding of others. Empathic changes are particularly evident after focal prefrontal cortex damage and closed head injury in adults, though early frontal lobe damage is also associated with poor empathic and social development. Although alterations in empathy have been studied in only a handful of neurologic samples thus far, it may be an important outcome variable of brain injury, particularly in patients’ adjustment to family, community and vocational settings. Treatment possibilities are presented, though more comprehensive research is needed.

The Moral Affiliations of Disgust A Functional MRI Study

Recent investigations in cognitive neuroscience have shown that ordinary human behavior is guided by emotions that are uniquely human in their experiential and interpersonal aspects. These “moral emotions” contribute importantly to human social behavior and derive from the neurobehavioral reorganization of the basic plan of emotions that pervade mammalian life. Disgust is one prototypic emotion with multiple domains that include viscerosomatic reaction patterns and subjective experiences linked to (a) the sensory properties of a class of natural stimuli, (b) a set of aversive experiences and (c) a unique mode of experiencing morality. In the current investigation, we tested the hypotheses that (a) the experience of disgust devoid of moral connotations (“pure disgust”) can be subjectively and behaviorally differentiated from the experience of disgust disguised in the moral emotion of “indignation” and that (b) pure disgust and indignation may have partially overlapping neural substrates. Thirteen normal adult volunteers were investigated with functional magnetic resonance imaging as they read a series of statements depicting scenarios of pure disgust, indignation, and neutral emotion. After the scanning procedure, they assigned one basic and one moral emotion to each stimulus from an array of six basic and seven moral emotions. Results indicated that (a) emotional stimuli may evoke pure disgust with or without indignation, (b) these different aspects of the experience of disgust could be elicited by a set of written statements, and (c) pure disgust and indignation recruited both overlapping and distinct brain regions, mainly in the frontal and temporal lobes. This work underscores the importance of the prefrontal and orbitofrontal cortices in moral judgment and in the automatic attribution of morality to social events. Human disgust encompasses a variety of emotional experiences that are ingrained in frontal, temporal, and limbic networks.

Morals and the human brain: A working model.

Morality has been at the center of informal talks and metaphysical discussions since the beginning of history. Recently, converging lines of evidence from evolutionary biology, neuroscience and experimental psychology have shown that morality is grounded in the brain. This article reviews the main lines of investigation indicating that moral behavior is a product of evolutionary pressures that shaped the neurobehavioral processes related to the selective perception of social cues, the experience of moral emotions and the adaptation of behavioral responses to the social milieu. These processes draw upon specific cortical-subcortical loops that organize social cognition, emotion and motivation into uniquely human forms of experience and behavior. We put forth a model of brain-behavior relationships underlying moral reasoning and emotion that accommodates the impairments of moral behavior observed in neuropsychiatric disorders. This model provides a framework for empirical testing with current methods of neurobehavioral analysis.

Normative observations on neuropsychological test performances in old age

As part of a study of dementia, 162 normal volunteers in the age range of 65-84 years were given a battery of nine neuropsychological tests assessing temporal orientation, short-term memory, language functions, and visuoperceptive capacity. When compared to subjects less than 65 years of age, the groups showed little evidence of generalized decline in cognitive function before the age of 80 years. The 80-84 years subgroup showed a higher overall failure rate on the tests than the younger subgroups. Nevertheless, 70% of all subjects in the 80-84 years subgroup made no more than one failure on the nine tests. There were substantial differences among the tests in respect to their sensitivity to the effects of aging. The largest decline in performance was shown on tests of short-term visual memory, serial digit learning, and facial recognition. The other verbal, memory, and visuoperceptive tests were performed well up to the age of 80 years. The findings are interpreted as providing limited support for the hypothesis that normal aging does not necessarily involve a general decline in level of cognitive functioning. The clinical application of the tests that were sensitive or insensitive to the effects of aging is considered.

Developmental Outcomes after Early Prefrontal Cortex Damage.

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

Nonhemorrhagic infarction of the thalamus Behavioral, anatomic, and physiologic correlates

We studied five patients with nonhemorrhagic thalamic infarction with neuropsychological tests, CT, and somatosensory evoked responses (SERs). The three patients with left thalamic lesions had abnormalities of language, memory, visuospatial processing, intellect, and personality—changes compatible with dementia. The two patients with right thalamic lesions were not aphasic and did not have verbal memory defects, but were otherwise comparable. Four lesions occurred in the tuberothalamic artery territory and one in the deep interpeduncular artery territory. SERs revealed a delay in the first negative peak after P14 in the tuberothalamic patients, and a delay in the third negative peak (N60 in all patients.

The dissociation of anterograde and retrograde amnesia in a patient with herpes encephalitis

Establishing the precise relationship between anterograde amnesia (AA) and retrograde amnesia (RA) has implications for psychological and neuroanatomical models of memory. Many patients have been described who demonstrate AA in conjunction with RA or who demonstrate AA with little, or no apparent, RA. Intact anterograde memory in conjunction with deficits on tasks of retrograde memory is rarely encountered. In this paper, we describe a young female patient (LD) whose RA is extremely severe when contrasted with her mild to moderate deficits on tasks of verbal anterograde memory. In addition, on tests of episodic and semantic autobiographical memory, LD appeared more impaired in her recall of specific episodes than of factual information about her past. The importance of this dissociation in RA for the episodic-semantic distinction and the possible role of visual imagery in recalling remote episodic events are discussed.

Frontal lobe damage in children and adults: A comparative review

Clinical and experimental studies of focal frontal lobe damage in children and adults are reviewed and analyzed. Although each literature has traditionally been treated separately, we argue that they share many common issues and that comparative analysis reveals both contrasting and complementary, findings that provide the foundation for a life‐span view of frontal lobe maturation and operation. Furthermore, each literature offers unique data regarding frontal lobe damage and recovery. Integration of these diverse findings is important to clinical and theoretical advances, and leads to the common view that the frontal lobes and their connections are critical to the development and maintenance of human adjustment and adaptive behavior throughout life.