Fifty Years of Prefrontal Cortex Research: Impact on Assessment

Our knowledge of the functions of the prefrontal cortex, often called executive, supervisory, or control, has been transformed over the past 50 years. After operationally defining terms for clarification, we review the impact of advances in functional, structural, and theoretical levels of understanding upon neuropsychological assessment practice as a means of identifying 11 principles/challenges relating to assessment of executive function. Three of these were already known 50 years ago, and 8 have been confirmed or emerged since. Key themes over this period have been the emergence of the use of naturalistic tests to address issues of "ecological validity"; discovery of the complexity of the frontal lobe control system; invention of new tests for clinical use; development of key theoretical frameworks that address the issue of the role of prefrontal cortex systems in the organization of human cognition; the move toward considering brain systems rather than brain regions; the advent of functional neuroimaging, and its emerging integration into clinical practice. Despite these huge advances, however, practicing neuropsychologists are still desperately in need of new ways of measuring executive function. We discuss pathways by which this might happen, including decoupling the two levels of explanation (information processing; brain structure) and integrating very recent technological advances into the neuropsychologist's toolbox. (JINS, 2017, 23, 755-767)

Altered Resting-State Functional Connectivity in Cortical Networks in Psychopathy

Psychopathy is a personality disorder characterized by callous antisocial behavior and criminal recidivism. Here we examine whether psychopathy is associated with alterations in functional connectivity in three large-scale cortical networks. Using fMRI in 142 adult male prison inmates, we computed resting-state functional connectivity using seeds from the default mode network, frontoparietal network, and cingulo-opercular network. To determine the specificity of our findings to these cortical networks, we also calculated functional connectivity using seeds from two comparison primary sensory networks: visual and auditory networks. Regression analyses related network connectivity to overall psychopathy scores and to subscores for the “factors” and “facets” of psychopathy: Factor 1, interpersonal/affective traits; Factor 2, lifestyle/antisocial traits; Facet 1, interpersonal; Facet 2, affective; Facet 3, lifestyle; Facet 4, antisocial. Overall psychopathy severity was associated with reduced functional connectivity between lateral parietal cortex and dorsal anterior cingulate cortex. The two factor scores exhibited contrasting relationships with functional connectivity: Factor 1 scores were associated with reduced functional connectivity in the three cortical networks, whereas Factor 2 scores were associated with heightened connectivity in the same networks. This dissociation was evident particularly in the functional connectivity between anterior insula and dorsal anterior cingulate cortex. The facet scores also demonstrated distinct patterns of connectivity. We found no associations between psychopathy scores and functional connectivity within visual or auditory networks. These findings provide novel evidence on the neural correlates of psychopathy and suggest that connectivity between cortical association hubs, such as the dorsal anterior cingulate cortex, may be a neurobiological marker of the disorder

Neuromodulation of Spatial Associations: Evidence from Choice Reaction Tasks During Transcranial Direct Current Stimulation

Various portions of human behavior and cognition are influenced by covert implicit processes without being necessarily available to intentional planning. Implicit cognitive biases can be measured in behavioral tasks yielding SNARC effects for spatial associations of numerical and non-numerical sequences, or yielding the implicit association test effect for associations between insect-flower and negative-positive categories. By using concurrent neuromodulation with transcranial direct current stimulation (tDCS), subthreshold activity patterns in prefrontal cortical regions can be experimentally manipulated to reduce implicit processing. Thus, the application of tDCS can test neurocognitive hypotheses on a unique neurocognitive origin of implicit cognitive biases in different spatial-numerical and non-numerical domains. However, the effects of tDCS are not only determined by superimposed electric fields, but also by task characteristics. To outline the possibilities of task-specific targeting of tDCS, task characteristics and instructions can be varied systematically when combined with neuromodulation. In the present thesis, implicit cognitive processes are assessed in different paradigms concurrent to left-hemispheric prefrontal tDCS to investigate a verbal processing hypothesis for implicit associations in general. In psychological experiments, simple choice reaction tasks measure implicit SNARC and SNARC-like effects as relative left-hand vs. right-hand latency advantages for responding to smaller number or ordinal sequence targets. However, different combinations of polarity-dependent tDCS with stimuli and task procedures also reveal domain-specific involvements and dissociations. Discounting previous unified theories on the SNARC effect, polarity-specific neuromodulation effects dissociate numbers and weekday or month ordinal sequences. By considering also previous results and patient studies, I present a hybrid and augmented working memory account and elaborate the linguistic markedness correspondence principle as one critical verbal mechanism among competing covert coding mechanisms. Finally, a general stimulation rationale based on verbal working memory is tested in separate experiments extending also to non-spatial implicit association test effects. Regarding cognitive tDCS effects, the present studies show polarity asymmetry and task-induced activity dependence of state-dependent neuromodulation. At large, distinct combinations of the identical tDCS electrode configuration with different tasks influences behavioral outcomes tremendously, which will allow for improved task- and domain-specific targeting

Progressive compromise of nouns and action verbs in posterior cortical atrophy

Processing of nouns and action verbs can be differentially compromised following lesions to posterior and anterior/motor brain regions, respectively. However, little is known about how these deficits progress in the course of neurodegeneration. To address this issue, we assessed productive lexical skills in a patient with posterior cortical atrophy (PCA) at two different stages of his pathology. On both occasions, he underwent a structural brain imaging protocol and completed semantic fluency tasks requiring retrieval of animals (nouns) and actions (verbs). Imaging results were compared with those of controls via voxel-based morphometry (VBM), whereas fluency performance was compared to age-matched norms through Crawford's t-tests. In the first assessment, the patient exhibited atrophy of more posterior regions supporting multimodal semantics (medial temporal and lingual gyri), together with a selective deficit in noun fluency. Then, by the second assessment, the patient's atrophy had progressed mainly toward fronto-motor regions (rolandic operculum, inferior and superior frontal gyri) and subcortical motor hubs (cerebellum, thalamus), and his fluency impairments had extended to action verbs. These results offer unprecedented evidence of the specificity of the pathways related to noun and action-verb impairments in the course of neurodegeneration, highlighting the latter's critical dependence on damage to regions supporting motor functions, as opposed to multimodal semantic processes.Fil: Steeb, Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; ArgentinaFil: García Cordero, Indira Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; ArgentinaFil: Huizing, Marjolein Catharina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; ArgentinaFil: Collazo, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; ArgentinaFil: Borovinsky, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; ArgentinaFil: Ferrari, Jesica. Instituto de Neurología Cognitiva; ArgentinaFil: Martínez Cuitiño Carricaburo, María Macarena. Universidad de Buenos Aires. Facultad de Psicología; Argentina. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; ArgentinaFil: Ibáñez Barassi, Agustín Mariano. Australian Research Council; Australia. Universidad Autónoma del Caribe; Colombia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina. Universidad Adolfo Ibañez; ChileFil: Sedeño, Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; ArgentinaFil: García, Adolfo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Instituto de Neurología Cognitiva. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt | Fundación Favaloro. Instituto de Neurociencia Cognitiva y Traslacional. Fundación Ineco Rosario Sede del Incyt; Argentina. Universidad Nacional de Cuyo; Argentin

Dissociable Neural Contributions To Prospection During Decisions About The Future

Humans often make decisions that involve tradeoffs between immediate and delayed consequences, and tend to devalue or discount future outcomes. This phenomenon, known as delay discounting, has several real-world implications. A high discounter, indicating more impulsive behavior, is more likely to engage in risky behavior such as smoking or gambling, while a low discounter, exhibiting more patient behavior, is more likely to attain better educational and financial outcomes. Recent studies demonstrate that under certain conditions, imagining the future reduces discounting. The goal of this thesis is to examine the cognitive role and neural basis of imagination during intertemporal choice, and investigate the mechanisms by which imagination influences decision-making. Chapter 2 examines how specific components of imagination modulate activity in specific nodes of the default mode network. We find that two components of imagination, construction and evaluation, distinctly activate the dorsal and ventral nodes of the default mode network, demonstrating separate modifiability and indicating a role for multiple processes underlying imagination. Chapter 3 extends this finding by examining activity in these nodes while participants are completing a choice task. Since tangibility and value are often confounded in intertemporal choice, we used our neural markers of construction and evaluation from Chapter 2 to disentangle these distinct components during choice. Though we find that activity in evaluative regions increases when individuals choose a delayed option, we also find greater activity in constructive regions when individuals choose a delayed outcome, indicating that chosen options are perhaps imagined more vividly than unchosen ones. Further, greater activity in constructive regions seems to be driven by high discounters, suggesting that higher discounters rely on vividness to a greater extent during choice than lower discounters. We extend this finding in Chapter 4 by investigating the effects of behavioral interventions of the constructive component on delay discounting. Surprisingly, we find that being a better visualizer is correlated with steeper discounting, and long-term training in visualization of personal future goals leads to greater impulsive behavior. Together, these findings advance our understanding of how specific imagination processes influence decision-making through differential neural activity, laying the groundwork for implementing targeted, personally-tailored future interventions to reduce risky behavior

The meditative mind: a comprehensive meta-analysis of MRI studies

Over the past decade mind and body practices, such as yoga and meditation, have raised interest in different scientific fields; in particular, the physiological mechanisms underlying the beneficial effects observed in meditators have been investigated. Neuroimaging studies have studied the effects of meditation on brain structure and function and findings have helped clarify the biological underpinnings of the positive effects of meditation practice and the possible integration of this technique in standard therapy. The large amount of data collected thus far allows drawing some conclusions about the neural effects of meditation practice. In the present study we used activation likelihood estimation (ALE) analysis to make a coordinate-based meta-analysis of neuroimaging data on the effects of meditation on brain structure and function. Results indicate that meditation leads to activation in brain areas involved in processing self-relevant information, self-regulation, focused problem-solving, adaptive behavior, and interoception. Results also show that meditation practice induces functional and structural brain modifications in expert meditators, especially in areas involved in self-referential processes such as self-awareness and self-regulation. These results demonstrate that a biological substrate underlies the positive pervasive effect of meditation practice and suggest that meditation techniques could be adopted in clinical populations and to prevent disease

Resting state glutamate predicts elevated pre-stimulus alpha during self-relatedness: A combined EEG-MRS study on 'rest-self' overlap.

Recent studies have demonstrated neural overlap between resting state activity and self-referential processing. This “rest-self” overlap occurs especially in anterior cortical midline structures like the perigenual anterior cingulate cortex (PACC). However, the exact neurotemporal and biochemical mechanisms remain to be identified. Therefore, we conducted a combined electroencephalography (EEG)-magnetic resonance spectroscopy (MRS) study. EEG focused on pre-stimulus (e.g., prior to stimulus presentation or perception) power changes to assess the degree to which those changes can predict subjects’ perception (and judgment) of subsequent stimuli as high or low self-related. MRS measured resting state concentration of glutamate, focusing on PACC. High pre-stimulus (e.g., prior to stimulus presentation or perception) alpha power significantly correlated with both perception of stimuli judged to be highly self-related and with resting state glutamate concentrations in the PACC. In sum, our results show (i) pre-stimulus (e.g., prior to stimulus presentation or perception) alpha power and resting state glutamate concentration to mediate rest-self overlap that (ii) dispose or incline subjects to assign high degrees of self-relatedness to perceptual stimuli

Negative mood-induction modulates default mode network resting-state functional connectivity in chronic depression

BACKGROUND: The aim of this study was to investigate the effects of sad mood on default mode network (DMN) resting-state connectivity in persons with chronic major depressive disorder (cMDD). METHODS: Participants with a diagnosis of cMDD (n=18) and age, gender and education level matched participants without a diagnosis of depression (n=18) underwent a resting-state fMRI scan, before and after a sad mood induction. The posterior cingulate cortex (PCC) was used as a seed for DMN functional connectivity across the two resting-state measurements. RESULTS: Mood ratings decreased in both groups following the sad mood induction procedure. PCC connectivity with the parahippocampal gyrus, the superior temporal gyrus and the anterior inferior temporal cortex increased in cMDD patients following the sad mood induction, whereas it decreased in non-patient controls. PCC connectivity with the anterior prefrontal cortex and the precuneus decreased in cMDD patients following the sad mood induction, whereas it increased in non-patient controls. LIMITATIONS: Limitations of this study include the relatively small sample size and lack of a clinical control group. CONCLUSIONS: These findings are in line with neurobiological models of depression suggesting that the observed changes in DMN connectivity following the sad mood induction might reflect a failure to exert cognitive control over negative memory retrieval in patients with cMDD