The impact of cerebral embolization during infant cardiac surgery on neurodevelopmental outcomes at intermediate follow-up.

Cerebral embolization during pediatric cardiac surgery may be an underappreciated source of subsequent neurodevelopmental impairment. Transcranial Doppler ultrasound is a neuromonitoring tool that can provide intraoperative surveillance for cerebral embolization. We hypothesized that increased cerebral embolic signals detected during infant cardiac surgery would be associated with worse neurodevelopmental outcomes at follow-up. A study group of 24 children who underwent infant cardiac surgery with transcranial Doppler detection of cerebral embolic signals returned at intermediate follow-up for standardized neurodevelopmental assessment. The children were evaluated using two neurocognitive tests and the parents completed two questionnaires regarding observed behavior. Statistical analysis assessed for correlation between the number of cerebral embolic signals at surgery and the results of the neurodevelopmental assessment. Of the 67 test parameters analyzed, five showed a significant association with the number of embolic signals, yet, all in the contrary direction of the clinical hypothesis, likely representing a Type I error. Thus, in this small cohort of patients, the number of cerebral embolic signals detected during infant cardiac surgery was not shown to be associated with worse neurodevelopmental outcomes at intermediate follow-up. A larger study is probably necessary to ascertain the potential influence of cerebral embolic signals on eventual neurologic outcomes in children. The clinical relevance of cerebral embolic signals during pediatric cardiac surgery remains undetermined and deserves further investigation.

Roles of Education and IQ in Cognitive Reserve in Parkinson's Disease-Mild Cognitive Impairment.

BACKGROUND/AIMS: The role of cognitive reserve in Parkinson's disease (PD)-mild cognitive impairment (MCI) is incompletely understood. METHODS: The relationships between PD-MCI, years of education, and estimated premorbid IQ were examined in 119 consecutive non-demented PD patients using logistic regression models. RESULTS: Higher education and IQ were associated with reduced odds of PD-MCI in univariate analysis. In multivariable analysis, a higher IQ was associated with a significantly decreased odds of PD-MCI, but education was not. CONCLUSION: The association of higher IQ and decreased odds of PD-MCI supports a role for cognitive reserve in PD, but further studies are needed to clarify the interaction of IQ and education and the impact of other contributors such as employment and hobbies.

Metacognitive deficits in frontotemporal dementia.

OBJECTIVES: To investigate whether metacognitive impairments in self-awareness and self-monitoring occur in patients with frontotemporal dementia (FTD), particularly among those with prominent social and dysexecutive impairments. METHODS: Patients diagnosed with FTD were divided by clinical subtype (social-dysexecutive (n = 12) aphasic (n = 15), and constituent subgroups of progressive non-fluent aphasia and semantic dementia) and compared with subjects with probable Alzheimer's disease (AD, n = 11) and age-matched healthy controls (n = 11). All subjects completed comprehensive behavioural ratings scales, which were compared with caregiver ratings. Subjects also rated their test performances in verbal associative fluency, word list learning, and memory task with comparisons made between actual and judged performance levels. RESULTS: The FTD sample as a whole showed significantly less behavioural self-awareness and self-knowledge than the AD and healthy control samples. FTD patients with prominent social and dysexecutive impairments demonstrated the most extensive loss of self-awareness and self-knowledge, significantly overrating themselves in multiple social, emotional, and cognitive domains, and failing to acknowledge that any behavioural change had occurred in most areas. The remaining clinical samples showed select and minimal discrepancies. All clinical groups were significantly unaware of their apathy levels. Most FTD patients judged episodic cognitive test performance adequately, with partial difficulties observed in the socially impaired and progressive non-fluent aphasia subgroups. CONCLUSIONS: FTD patients, particularly those with prominent social and dysexecutive impairments, exhibit profound metacognitive anosognosia that may represent a loss of self-awareness, self-monitoring, and self-knowledge, likely related to significant prefrontal pathophysiology. Other FTD clinical groups and AD patients showed less pervasive and more select metacognitive deficiencies.

Frontopolar and anterior temporal cortex activation in a moral judgment task: preliminary functional MRI results in normal subjects.

OBJECTIVE: To study the brain areas which are activated when normal subjects make moral judgments. METHOD: Ten normal adults underwent BOLD functional magnetic resonance imaging (fMRI) during the auditory presentation of sentences that they were instructed to silently judge as either "right" or "wrong". Half of the sentences had an explicit moral content ("We break the law when necessary"), the other half comprised factual statements devoid of moral connotation ("Stones are made of water"). After scanning, each subject rated the moral content, emotional valence, and judgment difficulty of each sentence on Likert-like scales. To exclude the effect of emotion on the activation results, individual responses were hemodynamically modeled for event-related fMRI analysis. The general linear model was used to evaluate the brain areas activated by moral judgment. RESULTS: Regions activated during moral judgment included the frontopolar cortex (FPC), medial frontal gyrus, right anterior temporal cortex, lenticular nucleus, and cerebellum. Activation of FPC and medial frontal gyrus (BA 10/46 and 9) were largely independent of emotional experience and represented the largest areas of activation. CONCLUSIONS: These results concur with clinical observations assigning a critical role for the frontal poles and right anterior temporal cortex in the mediation of complex judgment processes according to moral constraints. The FPC may work in concert with the orbitofrontal and dorsolateral cortex in the regulation of human social conduct.

Abnormal Wada and neuropsychological testing results due to topiramate therapy.

A 46-year-old man experienced intractable seizures since childhood. Due to lack of response to antiepilepsy drugs (AEDs), he underwent a surgical evaluation that was consistent with seizure onset in the left medial temporal lobe. While on topiramate and carbamazepine, his preoperative neuropsychological scores and sodium amytal (Wada) scores were low and may have excluded him from surgery. Repeat testing on lamotrigine and carbamazepine showed improvement in his scores, allowing him to undergo surgery. Physicians must therefore be cautious in evaluating such test scores while a patient is on topiramate.

Hemispheric preference in visuospatial processing: a complementary approach with fMRI and lesion studies.

Historically, the left cerebral hemisphere has been considered specialized for language, whereas the right cerebral hemisphere is aligned with spatial processes. However, studies have called into question adherence to this model and suggested that both hemispheres participate in language and spatial cognition. Using functional Magnetic Resonance Imaging (fMRI) and human brain lesion studies, we determined whether these complementary techniques could clarify issues of hemispheric dominance. Using a modified Benton Judgement of Line Orientation (JLO) test, considered a relatively pure spatial processing task, we found robust and significant (p < 0.0005) bilateral superior parietal lobe activation on fMRI in ten right-handed male adult volunteers. This was corroborated by lesion data in a cohort of 17 patients who showed significant JLO impairments after either right or left parietal lobe damage, with right parietal damage associated with somewhat more severe deficit. Detailed wavelet analysis of the fMRI time-series did, however, reveal a more dominant role of the right parietal lobe in "kick-starting" the task. To our knowledge, this is a novel way of using fMRI to address functional hemispheric differences in a cognitive task that is known to have bilateral representation.

Effects of early onset brain injury on the development of cognition and behavior: introduction to the special issue.

The effects of brain injury acquired early in life on the development of cognition and behavior are not well understood. Deciphering these effects and modeling their neurodevelopmental trajectories are major concerns for clinicians and scientists. Historically, a prevailing notion has been that early-onset brain damage has a more favorable prognosis than does brain damage acquired in adulthood. However, there is growing evidence suggesting that early-onset damage to prefrontal brain structures may have devastating consequences on the emergence of adaptive behavior throughout development. Particularly prominent are disorders of personality, social behavior, and executive functions such as planning and decision making. This special issue presents a series of new empirical studies that address these issues in depth, from several different perspectives, and in both human and animal participants. The findings promise to shed further light on both the neurobiology of development, and diverse neurodevelopmental disorders. Such advances may also enhance clinical diagnosis and facilitate the design of more effective interventions to help reduce the tremendous burden that neurodevelopmental disorders place on personal well-being, family structure, educational systems, and social resources.

Adolescent neuropsychological development after early right prefrontal cortex damage.

Adolescent development and pattern of recovery are described for a 15-year-old boy who sustained extensive right dorsolateral prefrontal cortex damage at age 7 from rupture and surgical treatment of a deep arteriovenous malformation. Follow-up evaluations at 4 years and most recently 8 years after illness have shown clear improvement in social-behavioral and almost all cognitive areas initially assessed. He demonstrated resolution of left hemispatial neglect and other visuospatial impairments in working memory, design fluency, and planning and organization. However, at the 8-year follow-up interval, an acquired form of attention deficit disorder remains evident. We hypothesized that this is the likely cause of comparatively lower scores in general intelligence, verbal learning and memory, discourse, and processing speed, that at the 4-year follow-up interval. New measures of emotional face and voice recognition showed only minor difficulties, principally in identifying vocal disgust and fear. Social and psychological maturation has continued to improve, with no evidence of developmental arrest or pervasive social impairment, although the individual is confused at times by complexities and nuances of social interaction. The pattern of findings 8 years after early right dorsolateral prefrontal cortex damage suggests remarkable recovery of primary visuospatial and social impairments, but lingering and somewhat worsening performance deficits which may be due to attentional difficulties and impulsive responding. Treatment of the attentional difficulties is currently being investigated.

Taste perception in patients with insular cortex lesions.

Research on nonhuman primates suggests that the primary taste cortex in humans is located in the rostrodorsal insula. Qualitative and quantitative assessment of taste perception was performed on 6 patients with unilateral damage to the insula, 3 patients with brain damage outside the insula, and 11 age-matched, normal subjects. Each subject identified the quality and intensity of the gustatory stimuli applied separately to the left and right sides of the anterior tongue. Damage to the right insula produced ipsilateral taste recognition and intensity deficits. Damage to the left insula caused an ipsilateral deficit in taste intensity but a bilateral deficit in taste recognition. The unexpected deficit in the left-hemispheric stroke patients for taste recognition on the right side of the tongue suggests that taste information from both sides of the tongue passes through the left insula.

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.

Multi-gradient echo with susceptibility inhomogeneity compensation (MGESIC): demonstration of fMRI in the olfactory cortex at 3.0 T.

Short image acquisition times and sensitivity to magnetic susceptibility favor the use of gradient echo imaging methods in functional MRI (fMRI). However, magnetic susceptibility effects attributed to air-tissue interfaces also lead to severe signal loss in images of the large inferior frontal and lateral temporal cortices of the human brain, which renders these regions inaccessible to fMRI. The signal loss is caused by the local field gradients in the silce selection direction. A multigradient echo with magnetic susceptibility inhomogeneity compensation method (MGESIC) is proposed to overcome this problem. The MGESIC method effectively corrects the susceptibility artifacts and maintains the advantages of gradient echo methods to both BOLD sensitivity and fast image acquisition. The effectiveness of the MGESIC method is demonstrated by fMRI experimental results within the olfactory cortex.

Correlates of change in cognitive function in survivors from the Western Collaborative Group Study.

Changes in cognitive function were investigated in 566 subjects 65-86 years old at baseline, who are a subsample of the Western Collaborative Group Study, a cardiovascular epidemiologic study of middle-aged men that began in the 1960s. Cognitive function was assessed in 1986-1988 (baseline) and again in 1992-1994 by three standardized measures: the Benton Visual Retention Test, the Controlled Oral Word Association Test, and the Digit Symbol Substitution (DSS) Test. Longitudinal change in performance was defined as the shift over time in a subject's quartile rank ordering, using the baseline distribution of test scores as a standard. 'Decliners' and 'improvers' in cognitive function were subjects who lost or gained, respectively, two or more quartile ranks on all three tests combined. By this definition, 20% (n = 113) of subjects declined, compared with 17% (n = 95) who improved in cognitive performance from 1986-1988 to 1992-1994. After adjustment for age, education, and physical health, decline in cognitive performance was significantly associated with poor self-perceived health ratings, depression scale scores, and self-reports of physical activity. Rank score change in the DSS Test was the single best predictor of cognitive function at follow-up on a diverse battery of neuropsychological tests.

Distinctive forms of partial retrograde amnesia after asymmetric temporal lobe lesions: possible role of the occipitotemporal gyri in memory.

We tested the hypothesis that partial forms of retrograde amnesia were associated with highly asymmetric lesions to the inferior and anterior-medial temporal lobe. Postencephalitic subjects EK and DR were both impaired on standardized retrograde memory tests, but showed strikingly different profiles in cognitive tasks of name stem completion, name:face matching, temporal ordering, forced choice recognition, and occupational judgments of famous names and faces from the past 3 decades. EK sustained left inferior and anterior-medial temporal lobe lesion with a small right temporal polar lesion, and showed near-complete loss of retrieval, knowledge, and familiarity associated with famous names but minimal deficiencies with famous faces. DR sustained right inferior and anterior-medial temporal lobe lesion and showed a milder retrograde loss limited to utilizing famous face prompts in name stem completion, name:face matching, occupational judgments, and forced choice recognition. These impairments were also different from the memory retrieval deficit, but intact recognition shown by a case of ruptured anterior communicating artery aneurysm with presumed basal forebrain damage. We hypothesize that EK's extensive loss of famous name knowledge was related to left inferior temporal lobe damage, particularly in the lateral and medial occipitotemporal gyri. This region in the left temporal lobe may serve as a critical processing area for retrograde memory that permits activation of established semantic, temporal, and visual (i.e., facial) associations biographically dependent on the category of proper names. On the basis of connectional anatomy patterns in the nonhuman primate, this region receives extensive hippocampal output and is interconnected with the temporal polar region and cortical association areas, which have been implicated in retrieval and storage aspects of retrograde memory. In the right hemisphere, the occipitotemporal gyri may serve an important role in famous face processing as part of a bilateral neural network.

Impact of frontal lobe lesions on rehabilitation and recovery from acute brain injury.

The frontal lobe has been viewed historically in very different ways, ranging from enigmatic and mystifying to the crucial neural substrate for higher cognition and social behavior. Frontal lobe damage poses a unique and difficult set of challenges to the patient, their family and the neurorehabilitation team. Because of the role of the frontal lobe in adaptation and adjustment, such damage adversely affects a patient's participation in the process and content of rehabilitation. To aid diagnosis and treatment planning, a model of frontal lobe organization is outlined, focusing on the specific cognitive and behavioral symptom clusters associated with superior mesial, inferior mesial, dorsolateral and orbital frontal lesions. A taxonomy of social executive processes is presented for identifying impairments in social behavior and personality, based upon the domains of social self-regulation, social self-awareness, social-sensitivity (empathy), and social-salience. Specific interventions are described that encompass dopamine agonist therapy for blunted affect, mutism and akinesia, cognitive strategies for improving organization and planning deficits, and evolving treatments for social impairments.

Altered serial position learning after frontal lobe lesion.

The serial position function is a powerful and highly reliable feature of human learning, with well-described primacy and recency effects. We tested the hypothesis that frontal lobe lesions in patients would disrupt the serial position function since such patients are known to have disturbed temporal ordering, learning in the presence of interference, encoding and organizational approaches to learning. Performance was compared in patients with focal, acquired lesions of frontal and non-frontal cortices, using a standardized paradigm of verbal list learning. Results indicated a similar pattern of performance on first trial learning for the two groups. However, across learning trials, frontal lesion subjects failed to maintain significant primacy and recency effects. Non-frontal lesion subjects consistently showed the expected U-shaped serial position curve across all trials. Subjective organization in learning was particularly deficient in the dorsolateral frontal lesion subjects. We propose that serial position effects are qualitatively different after frontal lobe lesion, being transitory and prone to alteration by the cumulative effects of disturbed temporal-spatial processing across learning trials.

Nonverbal amnesia and asymmetric cerebral lesions following encephalitis.

Global amnesia after herpes simplex encephalitis has been typically associated with lesions of anterior and medial temporal lobe, inferior and medial frontal lobe, and insula. The neuropathologic correlates of this disease are usually considered to be bilateral and similar across cases. We describe a 27-year-old woman whose chronic amnesia and cerebral lesions after viral encephalitis indicate a different pattern. Two features distinguish her presentation: (1) markedly asymmetric lesions extensively involving the right temporal lobe but sparing almost all of the same structures on the left and (2) severe compromise of nonverbal learning and a nonverbal retrograde amnesia in contrast to disproportionately small impairments of verbal learning and retention. The findings suggest that encephalitis patients cannot be treated as a homogeneous group and that detailed analysis of variability in their anatomic lesions may be an important explanatory factor in neural accounts of these severe human amnesias.

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.

Long-term psychological consequences of childhood frontal lobe lesion in patient DT.

Patient DT was examined 26 years after she acquired focal frontal lobe damage at 7 years of age. This report focused on several aspects of psychological outcome, including the empirical study of social development into early adulthood. Standardized measures of empathy, psychosocial development, and personality were analyzed, along with a moral judgment interview and patterns of adult social behavior. Results indicated that DT has a very limited capacity for empathic understanding, inadequate identity development, difficulties in vocational adjustment, and a concrete level of moral reasoning. Her social behavior and profile of test scores suggest that social development and adaptation have been arrested at early adolescent levels. We conclude that early frontal lobe damage has profound effects on social development, and that the frontal lobes provide a crucial neural substrate for social maturation.

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.

"Frontal lobe" utilization behavior associated with paramedian thalamic infarction.

Disinhibited, exaggerated responses to objects and environmental cues (utilization behavior) occur predominantly with frontal lobe damage. We report a striking example associated with paramedian thalamic infarction suggesting a thalamofrontal component to environmental interactions that require inhibition, self-monitoring, and cognitive flexibility.