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.     

Apathy in frontotemporal dementia: behavioral and neuroimaging correlates

We investigated the occurrence of goal-directed motivational change in the form of apathy in patients with frontotemporal dementia (FTD), particularly those with behavioral variant social and executive deficits (bvFTD). Standardized behavioral inventory was employed to survey and compare apathy ratings from patients and caregivers. In cases of bvFTD, apathy ratings were further related to measures of social cognition, executive function, and atrophy on brain MRI. Results indicated that caregivers rated bvFTD patients as having significantly elevated apathy scores though patient self-ratings were normal. Caregiver and self-ratings of FTD samples with progressive nonfluent aphasia and semantic dementia did not differ from healthy controls and their informants. In the bvFTD sample, caregiver apathy scores were not correlated with general cognitive screening or depression scores, but were significantly correlated with social cognition and executive function measures. Voxel-based morphometry revealed that apathy ratings in bvFTD were related to prominent atrophy in the right caudate (including the ventral striatum), the right temporo-parietal junction, right posterior inferior and middle temporal gyri, and left frontal operculum- anterior insula region. Findings suggest that bvFTD is associated with a significant breakdown in goal-directed motivated behavior involving disruption of cortical-basal ganglia circuits that is also related to social and executive function deficits.     

Biopsychosocial Influences That Promote and Impede Social Brain Maturation

ABSTRACT

Social, emotional, and executive function systems of the brain change greatly during adolescence as the result of biopsychosocial influences. These factors alter the course of adolescent behavior through effects on the component processes of social behavior. Specifically, the influences of chronic stress, social and economic adversity, alcohol and drugs, and brain injury as well as parental buffering and support, increased neural connectivity and mentalizing resources, and enriched environments can impede or promote maturation of the social and executive brain networks that regulate social adjustment and emotional expression. Hence, there are many early “windows of opportunity” to affect the biological and neurocognitive foundations of adolescent social executive functions such as empathy, theory of mind, self-monitoring, and social emotions.     

Perceptual-attentional and motor-intentional bias in near and far space

Spatial bias demonstrated in tasks such as line-bisection may stem from perceptual-attentional (PA) "where" and motor-intentional (MI) "aiming" influences. We tested normal participants' line bisection performance in the presence of an asymmetric visual distracter with a video apparatus designed to dissociate PA from MI bias. An experimenter stood as a distractor to the left or right of a video monitor positioned in either near or far space, where participants viewed lines and a laser point they directed under (1) natural and (2) mirror-reversed conditions. Each trial started with the pointer positioned at either the top left or top right corner of the screen, and alternated thereafter. Data analysis indicated that participants made primarily PA leftward errors in near space, but not in far space. Furthermore, PA, but not MI, bias increased bilaterally in the direction of distraction. In contrast, MI, but not PA, bias was shifted bilaterally in the direction of startside. Results support the conclusion that a primarily PA left sided bias in near space is consistent with right hemisphere spatial attentional dominance. A bottom-up visual distractor specifically affected PA "where" spatial bias while top-down motor cuing influenced MI "aiming" bias.     

Olfactory dysfunction in man: anatomical and behavioral aspects

We reviewed studies examining the olfaction of patients with brain damage for the purpose of discerning correlations between disordered structure and function. Patient samples included those with neurological disorders and neurosurgical interventions and recording of spontaneous or elicited neuronal activity. Brain areas involved in olfaction include the olfactory bulbs, the orbitofrontal and medial temporal cortices, the thalamus, and the amygdala. Despite recent advances in olfactory anatomy, understanding of how these structures are related to olfactory detection, discrimination, and recognition continues to be limited. Inadequate localization of brain lesions and lack of comprehensive behavioral assessment have thus far prevented a detailed account of the organization of olfaction in the human brain.     

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.     

Child and Caregiver Dropout in Child Psychotherapy for Trauma

This study focused on the identification of variables collected at baseline assessments that predict children and caregivers who are at risk for dropout from treatment. A sample of 115 children and their caregivers who received evidence-based treatment for traumatic stress was utilized for this study. Multinomial logistic regression analyses indicated that caregiver and child age, the child's externalizing behaviors, and the child and caregiver's acknowledgment of posttraumatic stress symptoms significantly predicted premature dropout from treatment. Clarification of child and caregiver characteristics that increase the risk of dropout allows for the identification of families in need of additional support to stay in treatment.     

Developmental shifts in fMRI activations during visuospatial relational reasoning

To investigate maturational plasticity of fluid cognition systems, functional brain imaging was undertaken in healthy 8-19 year old participants while completing visuospatial relational reasoning problems similar to Raven's matrices and current elementary grade math textbooks. Analyses revealed that visuospatial relational reasoning across this developmental age range recruited activations in the superior parietal cortices most prominently, the dorsolateral prefrontal, occipital-temporal, and premotor/supplementary cortices, the basal ganglia, and insula. There were comparable activity volumes in left and right hemispheres for nearly all of these regions. Regression analyses indicated increasing activity predominantly in the superior parietal lobes with developmental age. In contrast, multiple anterior neural systems showed significantly less activity with age, including dorsolateral and ventrolateral prefrontal, paracentral, and insula cortices bilaterally, basal ganglia, and particularly large clusters in the midline anterior cingulate/medial frontal cortex, left middle cingulate/supplementary motor cortex, left insula-putamen, and left caudate. Findings suggest that neuromaturational changes associated with visuospatial relational reasoning shift from a more widespread fronto-cingulate-striatal pattern in childhood to predominant parieto-frontal activation pattern in late adolescence.     

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.