Frank Krueger

Executive dysfunction in frontotemporal dementia and corticobasal syndrome

Objective: To determine the pattern of executive dysfunction in frontotemporal dementia (FTD) and corticobasal syndrome (CBS) and to determine the brain areas associated with executive dysfunction in these illnesses. Method: We administered the Delis-Kaplan Executive Function System (D-KEFS), a collection of standardized executive function tests, to 51 patients with behavioral-variant FTD and 50 patients with CBS. We also performed a discriminant analysis on the D-KEFS to determine which executive function tests best distinguished the clinical diagnoses of FTD and CBS. Finally, we used voxel-based morphometry (VBM) to determine regional gray matter volume loss associated with executive dysfunction. Results: Patients with FTD and patients with CBS showed executive dysfunction greater than memory dysfunction. Executive function was better preserved in the patients with CBS than the patients with FTD with the exception of tests that required motor, visuospatial ability, or both. In patients with CBS, dorsal frontal and parietal and temporal-parietal cortex was associated with executive function. In FTD, tests with a language component (Verbal Fluency) were associated with left perisylvian cortex, sorting with the left dorsolateral prefrontal cortex, and reasoning (the Twenty Questions task) with the left anterior frontal cortex. The Twenty Questions test best distinguished the clinical diagnoses of CBS and FTD. Conclusions: The neuroanatomic findings (especially in frontotemporal dementia [FTD]) agree with the previous literature on this topic. Patients with FTD and patients with corticobasal syndrome (CBS) show disparate performance on higher-order executive functions, especially the Twenty Questions test. It may be difficult to distinguish motor and visuospatial ability from executive function in patients with CBS using tests with significant motor and visuospatial demands such as Trail Making.

Developmental effects of aggressive behavior in male adolescents assessed with structural and functional brain imaging

Aggressive behavior is common during adolescence. Although aggression-related functional changes in the ventromedial prefrontal cortex (vmPFC) and frontopolar cortex (FPC) have been reported in adults, the neural correlates of aggressive behavior in adolescents, particularly in the context of structural neurodevelopment, are obscure. We used functional and structural magnetic resonance imaging (MRI) to measure the blood oxygenation level-depended signal and cortical thickness. In a block-designed experiment, 14-17-year old adolescents imagined aggressive and non-aggressive interactions with a peer. We show reduced vmPFC activation associated with imagined aggressive behavior as well as enhanced aggression-related activation and cortical thinning in the FPC with increasing age. Changes in FPC activation were also associated with judgments of the severity of aggressive acts. Reduced vmPFC activation was associated with greater aggression indicating its normal function is to exert inhibitory control over aggressive impulses. Concurrent FPC activation likely reflects foresight of harmful consequences that result from aggressive acts. The correlation of age-dependent activation changes and cortical thinning demonstrates ongoing maturation of the FPC during adolescence towards a refinement of social and cognitive information processing that can potentially facilitate mature social behavior in aggressive contexts.

Normative database of judgment of complexity task with functional near infrared spectroscopy – Application for TBI

The ability to assess frontal lobe function in a rapid, objective, and standardized way, without the need for expertise in cognitive test administration might be particularly helpful in mild traumatic brain injury (TBI), where objective measures are needed. Functional near infrared spectroscopy (fNIRS) is a reliable technique to noninvasively measure local hemodynamic changes in brain areas near the head surface. In this paper, we are combining fNIRS and frameless stereotaxy which allowed us to co-register the functional images with previously acquired anatomical MRI volumes. In our experiment, the subjects were asked to perform a task, evaluating the complexity of daily life activities, previously shown with fMRI to activate areas of the anterior frontal cortex. We reconstructed averaged oxyhemoglobin and deoxyhemoglobin data from 20 healthy subjects in a spherical coordinate. The spherical coordinate is a natural representation of surface brain activation projection. Our results show surface activation projected from the medial frontopolar cortex which is consistent with previous fMRI results. With this original technique, we will construct a normative database for a simple cognitive test which can be useful in evaluating cognitive disability such as mild traumatic brain injury.

Fatty-acid amide hydrolase polymorphisms and post- traumatic stress disorder after penetrating brain injury

The past few years have seen an increase in the clinical awareness of post-traumatic stress disorder (PTSD), one of the most disabling and least understood behavioral disorders. Although the biological bases of PTSD are poorly understood, fatty-acid amide hydrolase (FAAH) activity has been linked with arousability and aversive-memories extinction, that is, two key features of PTSD. In this study, we investigated the association between the FAAH genetic polymorphisms and PTSD development and maintenance. We assessed PTSD frequency in a group of male Vietnam war veterans who suffered combat-related penetrating traumatic brain injury, that is, a relatively homogeneous population regarding the nature of the events that led to PTSD. We showed that rs2295633, a single-nucleotide polymorphism of FAAH, was significantly associated with PTSD diagnosis in subjects without lesions in the ventromedial prefrontal cortex. Moreover, the presence of the C allele was associated with more severe re-experiencing of trauma and more negative reported childhood experiences. In conclusion, our data suggest that FAAH has an important role in PTSD through modulation of aversive memories and point to both a novel therapeutic target and a possible risk marker for this condition.

Interest in politics modulates neural activity in the amygdala and ventral striatum.

Studies on political participation have found that a persons interest in politics contributes to the likelihood that he or she will be involved in the political process. Here, we looked at whether or not interest in politics affects patterns of brain activity when individuals think about political matters. Using functional magnetic resonance imaging (fMRI), we scanned individuals (either interested or uninterested in politics based on a self‐report questionnaire) while they were expressing their agreement or disagreement with political opinions. After scanning, participants were asked to rate each political opinion presented in the scanner for emotional valence and emotional intensity. Behavioral results showed that those political opinions participants agreed with were perceived as more emotionally intense and more positive by individuals interested in politics relative to individuals uninterested in politics. In addition, individuals interested in politics showed greater activation in the amygdala and the ventral striatum (ventral putamen) relative to individuals uninterested in politics when reading political opinions in accordance with their own views. This study shows that having an interest in politics elicits activations in emotion‐ and reward‐related brain areas even when simply agreeing with written political opinions. Hum Brain Mapp, 2010.

Inflexible information acquisition strategies mediate visuo-spatial reasoning in stabilized schizophrenia patients

Abstract Objectives. Cognitive deficits are of fundamental importance to the clinical picture of schizophrenia and are on the verge to be included as diagnostic criteria in the DSM-V. While focusing on information processing deficits, no emphasis has been put on whether patients’ deficits can be accounted for by maladaptive information acquisition strategy deployment. Methods. We tested 24 stabilized patients with schizophrenia and 25 matched controls in a visuo-spatial analogy task with graded difficulty. Eye movement recordings served to identify information acquisition strategies. Results. Patients compared to healthy controls showed slower reaction times in the easiest condition and higher error rates in the more difficult conditions. Eye movement recordings illustrated that overall mean fixation duration increased with increasing task difficulty in healthy controls only. Further, patients deployed a more efficient strategy (“constructive matching”) less often than healthy controls in the easier conditions. Conclusions. These results suggest that information acquisition strategies mediate visuo-spatial cognitive performance in schizophrenia. Patients adopt a less efficient strategy independently of task difficulty indicated by a characteristic behavioural pattern. Our results point to a powerful tool of improving patients’ performance in cognitively demanding tasks by training them in more flexible cognitive (e.g., information acquisition) strategy deployment.