Irene Cristofori

Cognitive decline in older adults with a history of traumatic brain injury

Traumatic brain injury (TBI) is an important public health problem with potentially serious long-term neurobehavioural sequelae. There is evidence to suggest that a history of TBI can increase a persons risk of developing Alzheimers disease. However, individuals with dementia do not usually have a history of TBI, and survivors of TBI do not invariably acquire dementia later in life. Instead, a history of traumatic brain injury, combined with brain changes associated with normal ageing, might lead to exacerbated cognitive decline in older adults. Strategies to increase or maintain cognitive reserve might help to prevent exacerbated decline after TBI. Systematic clinical assessment could help to differentiate between exacerbated cognitive decline and mild cognitive impairment, a precursor of Alzheimers disease, with important implications for patients and their families.

Traumatic brain injury and cognition

Traumatic brain injury (TBI) is a major cause of death and disability, and therefore an important health and socioeconomic problem for our society. Individuals surviving from a moderate to severe TBI frequently suffer from long-lasting cognitive deficits. Such deficits include different aspects of cognition such as memory, attention, executive functions, and awareness of their deficits. This chapter presents a review of the main neuropsychological and neuroimaging studies of patients with TBI. These studies found that patients evolve differently according to the severity of the injury, the mechanism causing the injury, and the lesion location. Further research is necessary to develop rehabilitation methods that enhance brain plasticity and recovery after TBI. In this chapter, we summarize current knowledge and controversies, focusing on cognitive sequelae after TBI. Recommendations from the Common Data Elements are provided, with an emphasis on diagnosis, outcome measures, and studies organization to make data more comparable across studies. Final considerations on neuroimaging advances, rehabilitation approaches, and genetics are described in the final section of the chapter.

Genetic polymorphisms and traumatic brain injury: the contribution of individual differences to recovery

Recovery after Traumatic Brain Injury (TBI) is variable, even for patients with similar severity of brain injury. Recent research has highlighted the contribution that genetic predisposition plays in determining TBI outcome. This review considers the potential for genetic polymorphisms to influence recovery of cognitive and social processes following TBI. Limitations and considerations that researchers should make when assessing the potential impact of polymorphisms on TBI outcome are also discussed. Understanding the genetic factors that support neuroplasticity will contribute to an understanding of the variation in outcome following injury and help to identify potential targets for rehabilitation.

White and gray matter contributions to executive function recovery after traumatic brain injury

Objective: We investigated the association between regional white and gray matter volume loss and performance on executive functions (EFs) in patients with penetrating traumatic brain injury (pTBI). Methods: We studied 164 pTBI patients and 43 healthy controls from the Vietnam Head Injury Study. We acquired CT scans for pTBI patients and divided them according to lesion localization (left and right prefrontal cortex [PFC]). We administered EF tests (Verbal Fluency, Trail Making, Twenty Questions) and used voxel-based lesion symptom mapping (VLSM) and group-based correlational and multiple regression analyses to examine the relative influence of gray and white matter lesions on EF recovery. Results: The VLSM analysis revealed that white and gray white matter lesions were associated with impaired EFs. In the left PFC lesion group, damage to the PFC gray matter, anterior corona radiata, and superior longitudinal fasciculus (SLF) were most correlated with functional recovery. Verbal Fluency, which involves a broad fronto-temporo-parietal network, was best predicted by SLF lesion volume. Trail Making and Twenty Questions, which is associated with more focal left frontal damage, was better predicted by PFC lesions. Conclusions: Our results indicated that white matter volume loss can be a superior predictor of recovery and a crucial factor driving clinical outcome in functions involving a broad network such as Verbal Fluency. White matter damage may place additional burden on recovery by deteriorating signal transmission between cortical areas within a functional network.

The effect of claustrum lesions on human consciousness and recovery of function

Crick and Koch proposed that the claustrum plays a crucial role in consciousness. Their proposal was based on the structure and connectivity of the claustrum that suggested it had a role in coordinating a set of diverse brain functions. Given the few human studies investigating this claim, we decided to study the effects of claustrum lesions on consciousness in 171 combat veterans with penetrating traumatic brain injuries. Additionally, we studied the effects of claustrum lesions and loss of consciousness on long-term cognitive abilities. Claustrum damage was associated with the duration, but not frequency, of loss of consciousness, indicating that the claustrum may have an important role in regaining, but not maintaining, consciousness. Total brain volume loss, but not claustrum lesions, was associated with long-term recovery of neurobehavioral functions. Our findings constrain the current understanding of the neurobehavioral functions of the claustrum and its role in maintaining and regaining consciousness.

Brain Regions Influencing Implicit Violent Attitudes: A Lesion-Mapping Study.

Increased aggression is common after traumatic brain injuries and may persist after cognitive recovery. Maladaptive aggression and violence are associated with dysfunction in the prefrontal and temporal cortex, but such dysfunctional behaviors are typically measured by explicit scales and history. However, it is well known that answers on explicit scales on sensitive topics—such as aggressive thoughts and behaviors—may not reveal true tendencies. Here, we investigated the neural basis of implicit attitudes toward aggression in humans using a modified version of the Implicit Association Task (IAT) with a unique sample of 112 Vietnam War veterans who suffered penetrating brain injury and 33 healthy controls who also served in combat in Vietnam but had no history of brain injury. We hypothesized that dorsolateral prefrontal cortex (dlPFC) lesions, due to the crucial role of the dlPFC in response inhibition, could influence performance on the IAT. In addition, we investigated the causal contribution of specific brain areas to implicit attitudes toward violence. We found a more positive implicit attitude toward aggression among individuals with lesions to the dlPFC and inferior posterior temporal cortex (ipTC). Furthermore, executive functions were critically involved in regulating implicit attitudes toward violence and aggression. Our findings complement existing evidence on the neural basis of explicit aggression centered on the ventromedial prefrontal cortex. These findings highlight that dlPFC and ipTC play a causal role in modulating implicit attitudes about violence and are crucially involved in the pathogenesis of aggressive behavior. SIGNIFICANCE STATEMENT Maladaptive aggression and violence can lead to interpersonal conflict and criminal behavior. Surprisingly little is known about implicit attitudes toward violence and aggression. Here, we used a range of techniques, including voxel-based lesion–symptom mapping, to examine the causal role of brain structures underpinning implicit attitudes toward aggression in a unique sample of combat veterans with traumatic brain injury. We found that damage to the dorsolateral prefrontal cortex (dlPFC) led to a more positive implicit attitude toward violence that under most normal situations would be considered inappropriate. These results suggest that treatments aimed at increasing cognitive control using cognitive behavioral therapies dependent on the intact dlPFC could treat aggressive and violent behavior.

Neural correlates of mystical experience.

Mystical experiences, or subjectively believed encounters with a supernatural world, are widely reported across cultures and throughout human history. Previous theories speculate that executive brain functions underpin mystical experiences. To evaluate causal hypotheses, structural studies of brain lesion are required. Previous studies suffer from small samples or do not have valid measures of cognitive functioning prior to injury. We investigated mystical experience among participants from the Vietnam Head Injury Study and compared those who suffered penetrating traumatic brain injury (pTBI; n=116) with matched healthy controls (HC; n=32). Voxel-based lesion-symptom mapping analysis showed that lesions to frontal and temporal brain regions were linked with greater mystical experiences. Such regions included the dorsolateral prefrontal cortex (dlPFC) and middle/superior temporal cortex (TC). In a confirmatory analysis, we grouped pTBI patients by lesion location and compared mysticism experiences with the HC group. The dlPFC group presented markedly increased mysticism. Notably, longitudinal analysis of pre-injury data (correlating with general intelligence and executive performance) excludes explanations from individual differences. Our findings support previous speculation linking executive brain functions to mystical experiences, and reveal that executive functioning (dlPFC) causally contributes to the down-regulation of mystical experiences.

The Neural Bases for Devaluing Radical Political Statements Revealed by Penetrating Traumatic Brain Injury

Given the determinant role of ventromedial prefrontal cortex (vmPFC) in valuation, we examined whether vmPFC lesions also modulate how people scale political beliefs. Patients with penetrating traumatic brain injury (pTBI; N = 102) and healthy controls (HCs; N = 31) were tested on the political belief task, where they rated 75 statements expressing political opinions concerned with welfare, economy, political involvement, civil rights, war and security. Each statement was rated for level of agreement and scaled along three dimensions: radicalism, individualism and conservatism. Voxel-based lesion-symptom mapping (VLSM) analysis showed that diminished scores for the radicalism dimension (i.e. statements were rated as less radical than the norms) were associated with lesions in bilateral vmPFC. After dividing the pTBI patients into three groups, according to lesion location (i.e. vmPFC, dorsolateral prefrontal cortex [dlPFC] and parietal cortex), we found that the vmPFC, but not the dlPFC, group had reduced radicalism scores compared with parietal and HC groups. These findings highlight the crucial role of the vmPFC in appropriately valuing political behaviors and may explain certain inappropriate social judgments observed in patients with vmPFC lesions.

Biological and cognitive underpinnings of religious fundamentalism

&NA; Beliefs profoundly affect peoples lives, but their cognitive and neural pathways are poorly understood. Although previous research has identified the ventromedial prefrontal cortex (vmPFC) as critical to representing religious beliefs, the means by which vmPFC enables religious belief is uncertain. We hypothesized that the vmPFC represents diverse religious beliefs and that a vmPFC lesion would be associated with religious fundamentalism, or the narrowing of religious beliefs. To test this prediction, we assessed religious adherence with a widely‐used religious fundamentalism scale in a large sample of 119 patients with penetrating traumatic brain injury (pTBI). If the vmPFC is crucial to modulating diverse personal religious beliefs, we predicted that pTBI patients with lesions to the vmPFC would exhibit greater fundamentalism, and that this would be modulated by cognitive flexibility and trait openness. Instead, we found that participants with dorsolateral prefrontal cortex (dlPFC) lesions have fundamentalist beliefs similar to patients with vmPFC lesions and that the effect of a dlPFC lesion on fundamentalism was significantly mediated by decreased cognitive flexibility and openness. These findings indicate that cognitive flexibility and openness are necessary for flexible and adaptive religious commitment, and that such diversity of religious thought is dependent on dlPFC functionality. HighlightsWe examined religious fundamentalism in a large sample of penetrating TBI patients.Patients with VMPFC lesions reported greater fundamentalism.DLPFC lesions increase fundamentalism by reducing cognitive flexibility and openness.

The politics of insight

Previous studies showed that liberals and conservatives differ in cognitive style. Liberals are more flexible, and tolerant of complexity and novelty, whereas conservatives are more rigid, are more resistant to change, and prefer clear answers. We administered a set of compound remote associate problems, a task extensively used to differentiate problem-solving styles (via insight or analysis). Using this task, several researches have proven that self-reports, which differentiate between insight and analytic problem-solving, are reliable and are associated with two different neural circuits. In our research we found that participants self-identifying with distinct political orientations demonstrated differences in problem-solving strategy. Liberals solved significantly more problems via insight instead of in a step-by-step analytic fashion. Our findings extend previous observations that self-identified political orientations reflect differences in cognitive styles. More specifically, we show that type of political orientation is associated with problem-solving strategy. The data converge with previous neurobehavioural and cognitive studies indicating a link between cognitive style and the psychological mechanisms that mediate political beliefs.