Multifocal hypometabolic correlates to deficits of verbal memory in mesial temporal lobe epilepsy.

BACKGROUND AND OBJECTIVES: Neuropsychological research on mesial temporal lobe epilepsy (MTLE) often highlights material-specific memory deficits, but a lesion-focused model may not accurately reflect the underlying networks that support episodic memory in these patients. Our study evaluated the pathophysiology behind verbal learning/memory deficits as revealed by hypometabolism quantified through 18-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: This retrospective study included thirty presurgical patients with intractable unilateral MTLE who underwent interictal FDG-PET and verbal memory assessment (12 females, mean age: 38.73 years). Fluorodeoxyglucose-positron emission tomography mapping was performed with voxel-based mapping of glucose utilization to a database of age-matched controls to derive regional Z-scores. Neuropsychological outcome variables included scores on learning and recall trials of two distinct verbal memory measures validated for use in epilepsy research. Pearson's correlations evaluated relationships between clinical variables and verbal memory. Linear regression was used to relate regional hypometabolism and verbal memory assessment. Post hoc analyses assessed areas of FDG-PET hypometabolism (threshold Z ≤ -1.645 below mean) where verbal memory was impaired. RESULTS: Verbal memory deficits correlated with hypometabolism in limbic structures ipsilateral to language dominance but also correlated with hypometabolism in networks involving the ipsilateral perisylvian cortex and contralateral limbic and nonlimbic structures. DISCUSSION: We conclude that traditional models of verbal memory may not adequately capture cognitive deficits in a broader sample of patients with MTLE. This study has important implications for epilepsy surgery protocols that use neuropsychological data and FDG-PET to draw conclusions about surgical risks.

Rey-Osterrieth complex figure normative data for the psychiatric population.

Objective: Appropriate normative data are crucial for competent neuropsychological assessment. Although individuals with psychiatric illness often perform more poorly than healthy adults on neuropsychological testing, data that reflect the psychiatric population are often lacking. We present a normative dataset and calculation tools for the Rey-Osterrieth Complex Figure Test (RCFT) derived from the psychiatric inpatient population. Method: A sample of 301 psychiatric inpatients completed the RCFT and the Test of Memory Malingering (TOMM) between 1999 and 2018. Participants were 59.5% male, 82.1% Caucasian, 13.3% black, and 4.6% identified as another racial demographic, largely consistent with recent Substance Abuse and Mental Health Services Administration (2018) data for inpatients in U.S. psychiatric facilities. Scores for RCFT Copy, Short-Delay Free Recall, Long-Delay Free Recall, Total Recognition, and Percent Retained were modeled via multiple regression with age and education as predictors. Base rates were computed for subscores comprising Total Recognition to aid clinical decision making. Results: Age and education served as significant individual predictors for all models except one model predicting percent retained across delay that included only age. Regression equations and regression standard errors were used to produce a score calculator using a commonly available spreadsheet software package. Healthy adult norms under-estimated performance in our sample, underscoring the importance of these normative data. Conclusions: These normative data for the RCFT represent a large cohort of psychiatric inpatients. For clinical practice and research, both the data and the tools provided are likely to be of particular usefulness among individuals with serious mental illness.

Dissociation of Executive and Attentional Elements of the Digit Span Task in a Population of Older Adults: A Latent Class Analysis.

The prevailing model for working memory proposes the existence of a "central executive" responsible for coordinating and prioritizing incoming information from sensory and association cortices. The Digit Span task is commonly used by clinicians to parse attentional and executive components of working memory; however, the interrelatedness of these constructs in the context of advanced age and neurodegenerative disease remains an area of active investigation. The current study details a procedure and rationale for the use of latent class analysis, a data-driven, person-centered method, in the investigation of older adults and dementia. Class analysis of digit span performance in older adults (n = 874) drawn from a specialty clinic revealed four classes with distinct performance across task subcomponents. In three of the classes, attentional and executive elements demonstrated similar performance. The fourth class and implications of class structure are discussed in the context of aging.

A Systematic Review of Positron Emission Tomography of Tau, Amyloid Beta, and Neuroinflammation in Chronic Traumatic Encephalopathy: The Evidence To Date.

Chronic traumatic encephalopathy (CTE) is associated with pathological changes, yet detecting these changes during life has proven elusive. Positron emission tomography (PET) offers the potential for identifying such pathology. Few studies have been completed to date and their approaches and results have been diverse. It was the objective of this review to systematically examine relevant research using ligands for PET that bind to identified pathology in CTE. We focused on identification of patterns of binding and addressing gaps in knowledge of PET imaging for CTE. A comprehensive literature search was conducted. Data used were published on or before May 22, 2017. As the extant literature is limited, any peer-reviewed article assessing military, contact sports athletes, or professional fighters was considered for inclusion. The main outcomes were regional binding to brain regions identified through control comparisons or through clinical metrics (e.g., standardized uptake volume ratios). A total of 1207 papers were identified for review, of which six met inclusion criteria. Meta-analyses were planned but were deemed inappropriate given the small number of studies identified. Methodological concerns in these initial papers included small sample sizes, lack of a control comparison, use of nonstandard statistical procedures to quantify data, and interpretation of potentially off-target binding areas. Across studies, the hippocampi, amygdalae, and midbrain had reasonably consistent increased uptake. Evidence for increased uptake in cortical regions was less consistent. The evidence suggests that the field of PET imaging in those at risk for CTE remains nascent. As the field evolves to include more stringent studies, ligands for PET may prove an important tool in identifying CTE in vivo.

THE POSITIVITY OFFSET THEORY OF ANHEDONIA IN SCHIZOPHRENIA.

Prior studies have concluded that schizophrenia patients are not anhedonic because they do not report reduced experience of positive emotion to pleasant stimuli. The current study challenged this view by applying quantitative methods validated in the Evaluative Space Model of emotional experience to test the hypothesis that schizophrenia patients evidence a reduction in the normative "positivity offset" (i.e., the tendency to experience higher levels of positive than negative emotional output when stimulus input is absent or weak). Participants included 76 schizophrenia patients and 60 healthy controls who completed an emotional experience task that required reporting the level of positive emotion, negative emotion, and arousal to photographs. Results indicated that although schizophrenia patients evidenced intact capacity to experience positive emotion at high levels of stimulus input, they displayed a diminished positivity offset. Reductions in the positivity offset may underlie volitional disturbance, limiting approach behaviors toward novel stimuli in neutral environments.

The evaluation of insufficient cognitive effort in schizophrenia in light of low IQ scores.

Low IQ has recently been shown to predict neuropsychological effort test failure in healthy and neurological populations. Although low IQ is common in schizophrenia (SZ), its effect on effort test performance remains unclear in this population. The current study examined the role of IQ in effort test performance in a sample of 60 outpatients with SZ and 30 demographically matched healthy controls (CN). Participants were administered a battery of neuropsychological tests, and insufficient effort was calculated using two embedded effort indices: the Reliable Digit Span Effort Index and the Finger Tapping Effort Index. Results indicated that 16.1% of SZ patients and 0% CN failed both effort measures and that 32.1% of SZ and 3.3% of CN failed one measure. In SZ, IQ in the <70 or 70-79 range was associated with the highest rates of falling below the effort cut-off scores; however, patients with IQs in the low-average or higher range (>80) did not fall below effort cut-offs. Findings suggest that low IQ is a significant predictor of insufficient effort during neuropsychological test performance in schizophrenia, calling into question the validity of neuropsychological effort testing in SZ patients with low IQ.

Predicting psychosis across diagnostic boundaries: Behavioral and computational modeling evidence for impaired reinforcement learning in schizophrenia and bipolar disorder with a history of psychosis.

There is increasing evidence that schizophrenia (SZ) and bipolar disorder (BD) share a number of cognitive, neurobiological, and genetic markers. Shared features may be most prevalent among SZ and BD with a history of psychosis. This study extended this literature by examining reinforcement learning (RL) performance in individuals with SZ (n = 29), BD with a history of psychosis (BD+; n = 24), BD without a history of psychosis (BD-; n = 23), and healthy controls (HC; n = 24). RL was assessed through a probabilistic stimulus selection task with acquisition and test phases. Computational modeling evaluated competing accounts of the data. Each participant's trial-by-trial decision-making behavior was fit to 3 computational models of RL: (a) a standard actor-critic model simulating pure basal ganglia-dependent learning, (b) a pure Q-learning model simulating action selection as a function of learned expected reward value, and (c) a hybrid model where an actor-critic is "augmented" by a Q-learning component, meant to capture the top-down influence of orbitofrontal cortex value representations on the striatum. The SZ group demonstrated greater reinforcement learning impairments at acquisition and test phases than the BD+, BD-, and HC groups. The BD+ and BD- groups displayed comparable performance at acquisition and test phases. Collapsing across diagnostic categories, greater severity of current psychosis was associated with poorer acquisition of the most rewarding stimuli as well as poor go/no-go learning at test. Model fits revealed that reinforcement learning in SZ was best characterized by a pure actor-critic model where learning is driven by prediction error signaling alone. In contrast, BD-, BD+, and HC were best fit by a hybrid model where prediction errors are influenced by top-down expected value representations that guide decision making. These findings suggest that abnormalities in the reward system are more prominent in SZ than BD; however, current psychotic symptoms may be associated with reinforcement learning deficits regardless of a Diagnostic and Statistical Manual of Mental Disorders (5th Edition; American Psychiatric Association, 2013) diagnosis.

Emotion regulation abnormalities in schizophrenia: Directed attention strategies fail to decrease the neurophysiological response to unpleasant stimuli.

Previous research provides evidence that individuals with schizophrenia (SZ) have emotion regulation abnormalities, particularly when attempting to use reappraisal to decrease negative emotion. The current study extended this literature by examining the effectiveness of a different form of emotion regulation, directed attention, which has been shown to be effective at reducing negative emotion in healthy individuals. Participants included outpatients with SZ (n = 28) and healthy controls (CN: n = 25), who viewed unpleasant and neutral images during separate event-related potential and eye-movement tasks. Trials included both passive viewing and directed attention segments. During directed attention, gaze was directed toward highly arousing aspects of an unpleasant image, less arousing aspects of an unpleasant image, or a nonarousing aspect of a neutral image. The late positive potential (LPP) event-related potential component indexed emotion regulation success. Directing attention to nonarousing aspects of unpleasant images decreased the LPP in CN; however, SZ showed similar LPP amplitude when attention was directed toward more or less arousing aspects of unpleasant scenes. Eye tracking indicated that SZ were more likely than CN to attend to arousing portions of unpleasant scenes when attention was directed toward less arousing scene regions. Furthermore, pupilary data suggested that SZ patients failed to engage effortful cognitive processes needed to inhibit the prepotent response of attending to arousing aspects of unpleasant scenes when attention was directed toward nonarousing scene regions. Findings add to the growing literature indicating that individuals with SZ display emotion regulation abnormalities and provide novel evidence that dysfunctional emotion-attention interactions and generalized cognitive control deficits are associated with ineffective use of directed attention strategies to regulate negative emotion. (PsycINFO Database Record

Emotion regulation abnormalities in schizophrenia: cognitive change strategies fail to decrease the neural response to unpleasant stimuli.

Contrary to early conceptualizations of emotional experience in schizophrenia (SZ), recent research indicates that patients do not self-report less in-the-moment pleasure than controls (CN). Rather, patients report experiencing elevated levels of negative emotionality in response to a range of evocative stimuli. In this study, we examined the possibility that elevations in negative emotionality in SZ may reflect an underlying emotion regulation abnormality. Event-related potentials (ERPs) were recorded from outpatients with SZ (n = 25) and demographically matched healthy controls (n = 21) during passive viewing of unpleasant and neutral photographs. Unpleasant images were preceded by an audio description that described the image as being either negative or neutral. Neutral images were preceded by neutral audio descriptions. The late positive potential (LPP), an ERP component sensitive to cognitive change strategies, was examined as an index of emotion regulation. Both CN and SZ showed an increased LPP to negatively described unpleasant images compared with neutral images. In addition, CN showed evidence of emotion regulation, as reflected by a smaller LPP for unpleasant images preceded by a neutral descriptor, relative to a negative descriptor. In contrast, SZ patients showed an inability to downregulate emotional response, as evidenced by no difference in the amplitude of the LPP for unpleasant images preceded by negative or neutral descriptors. Findings provide neurophysiological evidence for an emotion regulation abnormality in SZ and suggest that failures in cognitive change may underlie increased negative emotionality in SZ.

Cognition-emotion interactions are modulated by working memory capacity in individuals with schizophrenia.

Prior research provides evidence for aberrant cognition-emotion interactions in schizophrenia. In the current study, we aimed to extend these findings by administering the "distractor devaluation" task to 40 individuals with schizophrenia and 32 demographically matched healthy controls. The task consisted of a simple visual search task for neutral faces, followed by an evaluative response made for one of the search items (or a novel item) to determine whether prior attentional selection results in a devaluation of a previously unattended stimulus. We also manipulated working memory demands by preceding the search array with a memory array that required subjects to hold 0, 1, or 2 items in working memory while performing the search array and devaluation task, to determine whether the normative process by which attentional states influence evaluative response is limited by working memory capacity. Results indicated that individuals with schizophrenia demonstrated the typical distractor devaluation effect at working memory load 0, suggesting intact evaluative response. However, the devaluation effect was absent at working memory loads of 1 and 2, suggesting that normal evaluative responses can be abolished in people with schizophrenia when working memory capacity is exceeded. Thus, findings provide further evidence for normal evaluative response in schizophrenia, but clarify that these normal experiences may not hold when working memory demands are too high.

Compromised decision making and the effects of manipulating physical states on human judgments.

OBJECTIVES: Nonmorally based decision making between two equitable objects often involves degrading the unchosen object and promoting the chosen object ("postdecisional dissonance"). One can extinguish these thought processes with the physical act of hand-washing ("clean slate" effects; [Lee & Schwarz (2010). Washing away postdecisional dissonance. Science, 328, 709.]). However, clean slate effects might not characterize all nonmorally based decision making, particularly for people who mentally "get stuck" making decisions (i.e., compromised decision making). DESIGN: We administered a clean slate task to 48 undergraduates (64.6% females; mean = 21.34 years, standard deviation = 4.06 years; 75% Caucasian), and identified individuals reporting relatively high-compromised versus low-compromised decision making (e.g., self-reported repetitive thought processes and generalized anxiety symptoms). RESULTS: Only individuals reporting relatively high-compromised decision making continued to express postdecisional dissonance even after hand-washing. CONCLUSIONS: Behavioral markers of clean slate effects might result in identifying phenotypes associated with psychological concerns typified by compromised decision making.