Neuropsychiatric outcomes following strokes involving the cerebellum: a retrospective cohort study.

Introduction: Given the wide-ranging involvement of cerebellar activity in motor, cognitive, and affective functions, clinical outcomes resulting from cerebellar damage can be hard to predict. Cerebellar vascular accidents are rare, comprising less than 5% of strokes, yet this rare patient population could provide essential information to guide our understanding of cerebellar function. Methods: To gain insight into which domains are affected following cerebellar damage, we retrospectively examined neuropsychiatric performance following cerebellar vascular accidents in cases registered on a database of patients with focal brain injuries. Neuropsychiatric testing included assessment of cognitive (working memory, language processing, and perceptual reasoning), motor (eye movements and fine motor control), and affective (depression and anxiety) domains. Results: Results indicate that cerebellar vascular accidents are more common in men and starting in the 5th decade of life, in agreement with previous reports. Additionally, in our group of twenty-six patients, statistically significant performance alterations were not detected at the group level an average of 1.3 years following the vascular accident. Marginal decreases in performance were detected in the word and color sub-scales of the Stroop task, the Rey Auditory Verbal Learning Test, and the Lafayette Grooved Pegboard Test. Discussion: It is well established that the acute phase of cerebellar vascular accidents can be life-threatening, largely due to brainstem compression. In the chronic phase, our findings indicate that recovery of cognitive, emotional, and affective function is likely. However, a minority of individuals may suffer significant long-term performance impairments in motor coordination, verbal working memory, and/or linguistic processing.

Hyperacute immune responses associate with immediate neuropathology and motor dysfunction in large vessel occlusions.

OBJECTIVE: Despite successful endovascular therapy, a proportion of stroke patients exhibit long-term functional decline, regardless of the cortical reperfusion. Our objective was to evaluate the early activation of the adaptive immune response and its impact on neurological recovery in patients with large vessel occlusion (LVO). METHODS: Nineteen (13 females, 6 males) patients with acute LVO were enrolled in a single-arm prospective cohort study. During endovascular therapy (EVT), blood samples were collected from pre and post-occlusion, distal femoral artery, and median cubital vein (controls). Cytokines, chemokines, cellular and functional profiles were evaluated with immediate and follow-up clinical and radiographic parameters, including cognitive performance and functional recovery. RESULTS: In the hyperacute phase (within hours), adaptive immune activation was observed in the post-occlusion intra-arterial environment (post). Ischemic vascular tissue had a significant increase in T-cell-related cytokines, including IFN-γ and MMP-9, while GM-CSF, IL-17, TNF-α, IL-6, MIP-1a, and MIP-1b were decreased. Cellularity analysis revealed an increase in inflammatory IL-17+ and GM-CSF+ helper T-cells, while natural killer (NK), monocytes and B-cells were decreased. A correlation was observed between hypoperfused tissue, infarct volume, inflammatory helper, and cytotoxic T-cells. Moreover, helper and cytotoxic T-cells were also significantly increased in patients with improved motor function at 3 months. INTERPRETATION: We provide evidence of the activation of the inflammatory adaptive immune response during the hyperacute phase and the association of pro-inflammatory cytokines with greater ischemic tissue and worsening recovery after successful reperfusion. Further characterization of these immune pathways is warranted to test selective immunomodulators during the early stages of stroke rehabilitation.

Large-scale lesion symptom mapping of depression identifies brain regions for risk and resilience.

Understanding neural circuits that support mood is a central goal of affective neuroscience, and improved understanding of the anatomy could inform more targeted interventions in mood disorders. Lesion studies provide a method of inferring the anatomical sites causally related to specific functions, including mood. Here, we performed a large-scale study evaluating the location of acquired, focal brain lesions in relation to symptoms of depression. Five hundred and twenty-six individuals participated in the study across two sites (356 male, average age 52.4 ± 14.5 years). Each subject had a focal brain lesion identified on structural imaging and an assessment of depression using the Beck Depression Inventory-II, both obtained in the chronic period post-lesion (>3 months). Multivariate lesion-symptom mapping was performed to identify lesion sites associated with higher or lower depression symptom burden, which we refer to as 'risk' versus 'resilience' regions. The brain networks and white matter tracts associated with peak regional findings were identified using functional and structural lesion network mapping, respectively. Lesion-symptom mapping identified brain regions significantly associated with both higher and lower depression severity (r = 0.11; P = 0.01). Peak 'risk' regions include the bilateral anterior insula, bilateral dorsolateral prefrontal cortex and left dorsomedial prefrontal cortex. Functional lesion network mapping demonstrated that these 'risk' regions localized to nodes of the salience network. Peak 'resilience' regions include the right orbitofrontal cortex, right medial prefrontal cortex and right inferolateral temporal cortex, nodes of the default mode network. Structural lesion network mapping implicated dorsal prefrontal white matter tracts as 'risk' tracts and ventral prefrontal white matter tracts as 'resilience' tracts, although the structural lesion network mapping findings did not survive correction for multiple comparisons. Taken together, these results demonstrate that lesions to specific nodes of the salience network and default mode network are associated with greater risk versus resiliency for depression symptoms in the setting of focal brain lesions.

Neural correlates of recognition and naming of famous persons and landmarks: A special role for the left anterior temporal lobe.

The anterior temporal lobes (ATLs) have been shown to be crucial for recognition and naming of unique entities such as persons and places. In this chapter, we review previous research that identified the neural underpinnings of these processes, and discuss the convergence zone theory of conceptual knowledge and proper name retrieval. Lesion-deficit and neuroimaging studies have found that the temporal poles are essential for recognition and naming of unique persons and places. Research has shown laterality, in that the right anterior temporal pole is specialized for recognition and the left for naming. Here, we analyzed recognition and naming of persons and landmarks in a large neurologic sample (N=244) using the Iowa Famous Faces and Famous Landmarks tests. For both categories, education had a significant effect on recognition and naming performances, but age and gender did not. Lesion-symptom maps revealed lower naming scores for both Faces and Landmarks associated with lesions to the anterior and mesial left temporal lobe. Lower recognition scores were also linked to left temporal lobe damage, possibly due to the method we used for measuring recognition (verbally based). Overall, the results demonstrate the importance of the temporal lobes for recognition and naming of unique persons and places.

Lesions in different prefrontal sectors are associated with different types of acquired personality disturbances.

"Frontal lobe syndrome" is a term often used to describe a diverse array of personality disturbances following frontal lobe damage. This study's guiding premise was that greater neuroanatomical specificity could be achieved by evaluating specific types of personality disturbances following acquired frontal lobe lesions. We hypothesized that three acquired personality disturbances would be associated with lesion involvement of distinct sectors of the prefrontal cortex (PFC): 1) emotional-social disturbance and ventromedial PFC, 2) hypoemotional disturbance and dorsomedial PFC, and 3) dysexecutive and dorsolateral PFC. In addition, we hypothesized that distressed personality disturbance would not be associated with focal PFC lesions in any sector. Each hypothesis was pre-registered and tested in 182 participants with adult-onset, chronic, focal brain lesions studied with an observational, cross-sectional design. Pre- and postmorbid personality was assessed by informant-rating with the Iowa Scales of Personality Change, completed by a spouse or family member. Two complementary analytic approaches were employed: 1) a hypothesis-driven region-of-interest (ROI) regression analysis examining the associations of lesions in specific PFC sectors with acquired personality disturbances; 2) a data-driven multivariate lesion-behavior mapping analysis, which was not limited to pre-specified regions. Each hypothesis received some support: (i) Emotional/social personality disturbance was most strongly associated with ventromedial PFC lesions in both statistical approaches. (ii) Hypoemotional disturbance was associated with dorsomedial PFC lesions in the ROI analyses, without any significant lesion-symptom mapping associations. (iii) Dysexecutive personality disturbance was associated with bilateral dorsolateral PFC lesions and ventromedial PFC lesions; lesion-symptom mapping showed maximal association of executive dysfunction with damage of the right middle frontal gyrus within the dorsolateral PFC. (iv) Distressed personality disturbance was not associated with lesions in any PFC sector. Altogether, the findings can be interpreted to indicate that damage to different prefrontal sectors may disrupt different anatomical-functional systems and result in distinct personality disturbances.

Lateralized differences for verbal learning across trials in temporal lobe epilepsy are not affected by surgical intervention.

This research aimed to broaden understanding of learning verbal material in participants with left- and right-sided mesial temporal lobe epilepsy (MTLE). We modeled word list-learning to determine how anterior temporal lobe resection affects verbal learning. Verbal learning (across trials) was assessed using the first five trials of the Rey Auditory Verbal Learning Test (RAVLT) in 128 participants with MTLE. Mixedeffects modeling was used to determine whether learning curves differed between participants with left- and right-sided MTLE pre- and post- anterior temporal lobe resection. Laterality of MTLE had a significant effect on both the model intercept and the linear slope, whereby participants with left-sided MTLE retained fewer words on both the first trial and on each subsequent trial than participants with right-sided MTLE; and this held regardless of anterior temporal lobe resection status (t(117) = -3.516, p < .001; t(120.50) = -2.049, p = .042, for intercept and linear slope, respectively). There were no significant differences in the learning curves after anterior temporal lobe resection surgery in either left- or right-sided MTLE. Our findings suggest that acquisition of verbal information may be especially impaired in patients with left-sided MTLE. Further, we show that verbal learning across trials was not affected by surgical intervention. This finding contributes to the broader understanding of the impacts of anterior temporal lobe resection on verbal memory function, and has important implications for the clinical management and surgical planning for patients with temporal lobe epilepsy.

Post-stroke outcomes predicted from multivariate lesion-behaviour and lesion network mapping.

Clinicians and scientists alike have long sought to predict the course and severity of chronic post-stroke cognitive and motor outcomes, as the ability to do so would inform treatment and rehabilitation strategies. However, it remains difficult to make accurate predictions about chronic post-stroke outcomes due, in large part, to high inter-individual variability in recovery and a reliance on clinical heuristics rather than empirical methods. The neuroanatomical location of a stroke is a key variable associated with long-term outcomes, and because lesion location can be derived from routinely collected clinical neuroimaging data there is an opportunity to use this information to make empirically based predictions about post-stroke deficits. For example, lesion location can be compared to statistically weighted multivariate lesion-behaviour maps of neuroanatomical regions that, when damaged, are associated with specific deficits based on aggregated outcome data from large cohorts. Here, our goal was to evaluate whether we can leverage lesion-behaviour maps based on data from two large cohorts of individuals with focal brain lesions to make predictions of 12-month cognitive and motor outcomes in an independent sample of stroke patients. Further, we evaluated whether we could augment these predictions by estimating the structural and functional networks disrupted in association with each lesion-behaviour map through the use of structural and functional lesion network mapping, which use normative structural and functional connectivity data from neurologically healthy individuals to elucidate lesion-associated networks. We derived these brain network maps using the anatomical regions with the strongest association with impairment for each cognitive and motor outcome based on lesion-behaviour map results. These peak regional findings became the 'seeds' to generate networks, an approach that offers potentially greater precision compared to previously used single-lesion approaches. Next, in an independent sample, we quantified the overlap of each lesion location with the lesion-behaviour maps and structural and functional lesion network mapping and evaluated how much variance each could explain in 12-month behavioural outcomes using a latent growth curve statistical model. We found that each lesion-deficit mapping modality was able to predict a statistically significant amount of variance in cognitive and motor outcomes. Both structural and functional lesion network maps were able to predict variance in 12-month outcomes beyond lesion-behaviour mapping. Functional lesion network mapping performed best for the prediction of language deficits, and structural lesion network mapping performed best for the prediction of motor deficits. Altogether, these results support the notion that lesion location and lesion network mapping can be combined to improve the prediction of post-stroke deficits at 12-months.

Cognitive and Psychological Functioning in Chiari Malformation Type I Before and After Surgical Decompression - A Prospective Cohort Study.

BACKGROUND: Chiari Malformation Type I (CM-I) is defined as cerebellar tonsil displacement more than 5 mm below the foramen magnum. This displacement can alter cerebrospinal fluid flow at the cervicomedullary junction resulting in Valsalva-induced headaches and syringomyelia and compress the brainstem resulting in bulbar symptoms. However, little is known about cognitive and psychological changes in CM-I. OBJECTIVE: To prospectively assess cognitive and psychological performance in CM-I and determine whether changes occur after surgical decompression. METHODS: Blinded evaluators assessed symptomatic CM-I patients ages ≥18 with a battery of neuropsychological and psychological tests. Testing was conducted preoperatively and 6 to 18 mo postoperatively. Data were converted to Z-scores based on normative data, and t-tests were used to analyze pre-post changes. RESULTS: A total of 26 patients were included, with 19 completing both pre- and post-op cognitive assessments. All patients had resolution of Valsalva-induced headaches and there was improvement in swallowing dysfunction (P < .0001), ataxia (P = .008), and sleep apnea (P = .021). Baseline performances in visual perception and construction (z = -1.11, P = .001) and visuospatial memory (z = -0.93, P = .002) were below average. Pre-post comparisons showed that CM-I patients had stable cognitive and psychological functioning after surgery, without significant changes from preoperative levels. CONCLUSION: CM-I patients had below average performance in visuospatial and visuoconstructional abilities preoperatively. Prospective longitudinal data following surgery demonstrated improved neurologic status without any decline in cognition or psychological functioning. Routine pre- and postoperative formal neuropsychological assessment in CM-I patients help quantify cognitive and behavioral changes associated with surgical decompression.

Assessing the Effects of Healthy and Neuropathological Aging on Personality with the Iowa Scales of Personality Change.

Personality changes in older adults with brain disease may be confounded by effects of normal aging. In this cross-sectional study, ratings with the Iowa Scales of Personality Change for 62 healthy older adults (OA-H, aged 60+) were compared to matched older adults with brain diseases (OA-BD). OA-H did not show any significant personality changes from middle age to older adulthood. However, between 10% and 20% of OA-H developed a disturbance in Lack of Stamina, Inflexibility, Lability, and Lack of Insight. Otherwise, the pattern of findings suggesting normal aging effects on personality disturbances in clinical groups are generally minimal.

Multivariate Lesion-Behavior Mapping of General Cognitive Ability and Its Psychometric Constituents.

General cognitive ability, or general intelligence (g), is central to cognitive science, yet the processes that constitute it remain unknown, in good part because most prior work has relied on correlational methods. Large-scale behavioral and neuroanatomical data from neurologic patients with focal brain lesions can be leveraged to advance our understanding of the key mechanisms of g, as this approach allows inference on the independence of cognitive processes along with elucidation of their respective neuroanatomical substrates. We analyzed behavioral and neuroanatomical data from 402 humans (212 males; 190 females) with chronic, focal brain lesions. Structural equation models (SEMs) demonstrated a psychometric isomorphism between g and working memory in our sample (which we refer to as g/Gwm), but not between g and other cognitive abilities. Multivariate lesion-behavior mapping analyses indicated that g and working memory localize most critically to a site of converging white matter tracts deep to the left temporo-parietal junction. Tractography analyses demonstrated that the regions in the lesion-behavior map of g/Gwm were primarily associated with the arcuate fasciculus. The anatomic findings were validated in an independent cohort of acute stroke patients (n = 101) using model-based predictions of cognitive deficits generated from the Iowa cohort lesion-behavior maps. The neuroanatomical localization of g/Gwm provided the strongest prediction of observed g in the new cohort (r = 0.42, p < 0.001), supporting the anatomic specificity of our findings. These results provide converging behavioral and anatomic evidence that working memory is a key mechanism contributing to domain-general cognition.SIGNIFICANCE STATEMENT General cognitive ability (g) is thought to play an important role in individual differences in adaptive behavior, yet its core processes remain unknown, in large part because of difficulties in making causal inferences from correlated data. Using data from patients with focal brain damage, we demonstrate that there is a strong psychometric correspondence between g and working memory - the ability to maintain and control mental information, and that the critical neuroanatomical substrates of g and working memory include the arcuate fasciculus. This work provides converging behavioral and neuroanatomical evidence that working memory is a key mechanism contributing to domain-general cognition.

Neural correlates of improvements in personality and behavior following a neurological event.

Research on changes in personality and behavior following brain damage has focused largely on negative outcomes, such as increased irritability, moodiness, and social inappropriateness. However, clinical observations suggest that some patients may actually show positive personality and behavioral changes following a neurological event. In the current work, we investigated neuroanatomical correlates of positive personality and behavioral changes following a discrete neurological event (e.g., stroke, benign tumor resection). Patients (N = 97) were rated by a well-known family member or friend on five domains of personality and behavior: social behavior, irascibility, hypo-emotionality, distress, and executive functioning. Ratings were acquired during the chronic epoch of recovery, when psychological status was stabilized. We identified patients who showed positive changes in personality and behavior in one or more domains of functioning. Lesion analyses indicated that positive changes in personality and behavior were most consistently related to damage to the bilateral frontal polar regions and the right anterior dorsolateral prefrontal region. These findings support the conclusion that improvements in personality and behavior can occur after a neurological event, and that such changes have systematic neuroanatomical correlates. Patients who showed positive changes in personality and behavior following a neurological event were rated as having more disturbed functioning prior to the event. Our study may be taken as preliminary evidence that improvements in personality and behavior following a neurological event may involve dampening of (premorbidly) more extreme expressions of emotion.

Acquired Personality Disturbances After Meningioma Resection Are Strongly Associated With Impaired Quality of Life.

BACKGROUND: Some patients experience long-term declines in quality of life following meningioma resection, but associated factors are not well understood. OBJECTIVE: To investigate whether long-term declines in quality of life (specifically impaired adaptive functioning) after meningioma resection are associated with specific personality disturbances that often develop with lesions in ventromedial prefrontal cortex (vmPFC). METHODS: We studied 38 patients who underwent resection of meningioma, 18 of whom had vmPFC lesions and 20 with lesions elsewhere (non-vmPFC). A total of 30 personality characteristics were rated by spouse or family, and a neuropsychologist blindly rated adaptive functioning an average of 3.8 yr postresection. Relevant personality disturbance was defined by a priori process: the presence of "conjoint personality disturbance" required specific disturbances in at least 2 of 4 types of disturbance: executive disorders, disturbed social behavior, emotional dysregulation, and hypoemotionality. RESULTS: Fourteen patients had impaired adaptive functioning: 12 had vmPFC lesions and 2 had non-vmPFC lesions. Fourteen patients had conjoint personality disturbance, and 12 of them had impaired adaptive functioning. By contrast, among the 24 patients who did not have conjoint personality disturbance, only 2 had impaired adaptive functioning. Mediation analysis showed that the association between vmPFC lesions and impaired adaptive functioning was mediated by the negative impact of acquired personality disturbance on adaptive functioning. CONCLUSION: Anterior skull base meningiomas plus resection surgery may result in specific personality disturbances that are highly associated with impaired adaptive functioning at long-term follow-up. These patients may benefit from early counseling regarding potential personality changes and their implications for adaptive functioning.

"Frontal lobe syndrome"? Subtypes of acquired personality disturbances in patients with focal brain damage.

Conceptualizations of the nature of acquired personality disturbances after brain damage, especially to prefrontal cortex, have progressed from clinical observations of a large, disparate set of disturbances to theories concerning neuroanatomically-based subgroups with prefrontal damage. However, hypothesized subtypes have not yet been studied systematically. Based on our previous investigations of acquired personality disturbances, we hypothesized five subtypes of acquired personality disturbances: Executive Disturbances, Disturbed Social Behavior, Emotional Dysregulation, Hypo-emotionality/De-Energization, and Distress, as well as an undisturbed group. Subtypes were investigated in 194 adults with chronic, stable, focal lesions located in various aspects of prefrontal lobes and elsewhere in the brain, using two different cluster analysis techniques applied to ratings on the Iowa Scales of Personality Change. One technique was a hypothesis-driven approach; the other was a set of strictly empirical analyses to assess the robustness of clusters found in the first analysis. The hypothesis-driven analysis largely supported the hypothesized set of subtypes. However, in contrast to the hypothesis, it suggested that disturbed social behavior and emotional dysregulation are not two distinct subtypes, but two aspects of one multifaceted type of disturbance. Additionally, the so-labeled "executive disturbances" group also showed disturbances in other domains. Results from the second (empirical) set of cluster analyses were consistent with findings from the hypothesis-driven cluster analysis. Overall, findings across the two cluster analyses indicated four subtypes of acquired personality disturbances: (1) executive disturbances in association with generalized disturbance, (2) dysregulation of emotions and behavior, (3) hypo-emotionality and de-energization, and (4) distress/anxiety. These findings show strong correspondence with subtypes suggested by prominent models of prefrontal systems based on neuroanatomically-defined circuits. Clarification of distinctive subtypes of acquired personality disturbances is a step toward enhancing our ability to tailor rehabilitative interventions for patients with prefrontal brain injuries.

The safety and efficacy of propofol as a replacement for amobarbital in intracarotid Wada testing of presurgical patients with epilepsy.

OBJECTIVE: The intracarotid sodium amytal procedure (the "Wada test") has for many years been the gold standard for language and memory lateralization and remains an important part of presurgical analysis for patients with medically intractable seizures. Due to shortages in the key sedative (amobarbital), neuropsychologists have turned to alternatives such as propofol. Our aim was to investigate the safety and efficacy of propofol relative to amobarbital in the Wada test. METHODS: We performed a retrospective review of the 97 Wada procedures performed at University of Iowa Hospitals and Clinics from 2007 through mid-2015. RESULTS: Propofol produced similar lateralization rates as amobarbital for both language and memory. Similar rates of patients in each group went on to have the resection surgery. With regard to safety, there were no differences found in average rate or severity of adverse effects. None of the demographic characteristics reviewed were predictive of increased risk for either drug. SIGNIFICANCE: These findings support previous studies indicating that propofol is as safe and efficacious as amobarbital, and can continue to be used in Wada procedures with confidence.

The cognitive and behavioral effects of meningioma lesions involving the ventromedial prefrontal cortex.

OBJECT Anterior skull base meningiomas are frequently associated with changes in personality and behavior. Although such meningiomas often damage the ventromedial prefrontal cortex (vmPFC), which is important for higher cognition, the cognitive and behavioral effects of these meningiomas remain poorly understood. Using detailed neuropsychological assessments in a large series of patients, this study examined the cognitive and behavioral effects of meningioma lesions involving the vmPFC. METHODS The authors reviewed neuropsychology and lesion mapping records of 70 patients who underwent resection of meningiomas. The patients were drawn from the Neurological Patient Registry at the University of Iowa. Patients were sorted into 2 groups: those with lesions involving the vmPFC and those with lesions that did not involve the vmPFC. Neuropsychological data pertaining to a comprehensive array of cognitive and behavioral domains were available preoperatively in 20 patients and postoperatively in all 70 patients. RESULTS No change occurred in basic cognitive functions (e.g., attention, perception, memory, construction and motor performance, language, or executive functions) from the preoperative to postoperative epochs for the vmPFC and non-vmPFC groups. There was a significant decline in the behavioral domain, specifically adaptive function, for both the vmPFC and non-vmPFC groups, and this decline was more pronounced for the vmPFC group. Additionally, postoperative data indicated that the vmPFC group had a specific deficit in value-based decision making, as evidenced by poor performance on the Iowa Gambling Task, compared with the non-vmPFC group. The vmPFC and non-vmPFC groups did not differ postoperatively on other cognitive measures, including intellect, memory, language, and perception. CONCLUSIONS Lesions of the vmPFC resulting from meningiomas are associated with specific deficits in adaptive function and value-based decision making. Meningioma patients showed a decline in adaptive function postoperatively, and this decline was especially notable in patients with vmPFC region meningiomas. Early detection and resection of meningiomas of the anterior skull base (involving the gyrus rectus) may prevent these deficits.

The left temporal pole is a heteromodal hub for retrieving proper names.

The left temporal pole (LTP) has been posited to be a heteromodal hub for retrieving proper names for semantically unique entities. Previous investigations have demonstrated that LTP is important for retrieving names for famous faces and unique landmarks. However, whether such a relationship would hold for unique entities apprehended through stimulus modalities other than vision has not been well established, and such evidence is critical to adjudicate claims about the "heteromodal" nature of the LTP. Here, we tested the hypothesis that the LTP would be important for naming famous voices. Individuals with LTP lesions were asked to recognize and name famous persons speaking in audio clips. Relative to neurologically normal and brain damaged comparison participants, patients with LTP lesions were able to recognize famous persons from their voices normally, but were selectively impaired in naming famous persons from their voices. The current results extend previous research and provide further support for the notion that the LTP is a convergence region serving as a heteromodal hub for retrieving the names of semantically unique entities.

Benefit of the doubt: a new view of the role of the prefrontal cortex in executive functioning and decision making.

The False Tagging Theory (FTT) is a neuroanatomical model of belief and doubt processes that proposes a single, unique function for the prefrontal cortex. Here, we review evidence pertaining to the FTT, the implications of the FTT regarding fractionation of the prefrontal cortex, and the potential benefits of the FTT for new neuroanatomical conceptualizations of executive functions. The FTT provides a parsimonious account that may help overcome theoretical problems with prefrontal cortex mediated executive control such as the homunculus critique. Control in the FTT is examined via the "heuristics and biases" psychological framework for human judgment. The evidence indicates that prefrontal cortex mediated doubting is at the core of executive functioning and may explain some biases of intuitive judgments.

A neuropsychological test of belief and doubt: damage to ventromedial prefrontal cortex increases credulity for misleading advertising.

We have proposed the False Tagging Theory (FTT) as a neurobiological model of belief and doubt processes. The theory posits that the prefrontal cortex is critical for normative doubt toward properly comprehended ideas or cognitions. Such doubt is important for advantageous decisions, for example in the financial and consumer purchasing realms. Here, using a neuropsychological approach, we put the FTT to an empirical test, hypothesizing that focal damage to the ventromedial prefrontal cortex (vmPFC) would cause a "doubt deficit" that would result in higher credulity and purchase intention for consumer products featured in misleading advertisements. We presented 8 consumer ads to 18 patients with focal brain damage to the vmPFC, 21 patients with focal brain damage outside the prefrontal cortex, and 10 demographically similar healthy comparison participants. Patients with vmPFC damage were (1) more credulous to misleading ads; and (2) showed the highest intention to purchase the products in the misleading advertisements, relative to patients with brain damage outside the prefrontal cortex and healthy comparison participants. The pattern of findings was obtained even for ads in which the misleading bent was "corrected" by a disclaimer. The evidence is consistent with our proposal that damage to the vmPFC disrupts a "false tagging mechanism" which normally produces doubt and skepticism for cognitive representations. We suggest that the disruption increases credulity for misleading information, even when the misleading information is corrected for by a disclaimer. This mechanism could help explain poor financial decision-making when persons with ventromedial prefrontal dysfunction (e.g., caused by neurological injury or aging) are exposed to persuasive information.

Dimensions of personality disturbance after focal brain damage: investigation with the Iowa Scales of Personality Change.

This study employed a multistep, rational-empirical approach to identify dimensions of personality disturbance in brain-damaged individuals: (a) Five dimensions were hypothesized based on empirical literature and conceptual grounds; (b) principal components analysis was performed on the Iowa Scales of Personality Change (ISPC) to determine the pattern of covariance among 30 personality characteristics; (c) when discrepancies existed between principal components analysis results and conceptually based dimensions, empirical findings and clinical considerations were weighed to determine assignment of ISPC scales to dimensions; (d) the fit of data to the refined dimensions was assessed by examination of intercorrelations; (e) differential predictions concerning the relationship of dimensions to ventromedial prefrontal cortex (vmPFC) damage were tested. This process resulted in the specification of five dimensions: Disturbed Social Behavior, Executive/Decision-Making Deficits, Diminished Motivation/Hypo-Emotionality, Irascibility, and Distress. In accord with predictions, the 28 participants with vmPFC lesions, compared to 96 participants with focal lesions elsewhere in the brain, had significantly more Disturbed Social Behavior and Executive/Decision-Making Deficits and tended to have more Diminished Motivation/Hypo-Emotionality. Irascibility was not significantly higher among the vmPFC group, and the groups had very similar levels of Distress. The findings indicate that conceptually distinctive dimensions with differential relationships to vmPFC can be derived from the Iowa Scales of Personality Change.

Neuroanatomical correlates of the Benton Facial Recognition Test and Judgment of Line Orientation Test.

Two of the most successful and widely used tests developed by Arthur Benton and colleagues are the Facial Recognition Test (FRT) and Judgment of Line Orientation Test (JLO), which probe visuoperceptual and visuospatial functions typically associated with right hemisphere structures, especially parietal, occipitoparietal, and occipitotemporal structures. Taking advantage of a large database of focal lesion patients (the Iowa Neurological Patient Registry), we used a new lesion-deficit mapping technique to investigate the neuroanatomical correlates of FRT and JLO performance. For the FRT, there were 201 patients with relevant data; of these, 38 were impaired on the FRT, and failure was most strongly associated with lesions in the right posterior-inferior parietal and right ventral occipitotemporal (fusiform gyrus) areas. For the JLO, there were 181 patients with relevant data; of these, 23 were impaired on the JLO, and failure was most strongly associated with lesions in the right posterior parietal region. These findings put new empirical teeth in the localizing value of the FRT and JLO tests, and they extend and sharpen previous work that had pointed to right posterior structures as being important for FRT and JLO performance