Adrianna Mendrek

Limbic abnormalities in affective processing by criminal psychopaths as revealed by functional magnetic resonance imaging

BACKGROUND Psychopathy is a complex personality disorder of unknown etiology. Central to the disorder are anomalies or difficulties in affective processing. METHODS Functional magnetic resonance imaging was used to elucidate the neurobiological correlates of these anomalies in criminal psychopaths during performance of an affective memory task. RESULTS Compared with criminal nonpsychopaths and noncriminal control participants, criminal psychopaths showed significantly less affect-related activity in the amygdala/hippocampal formation, parahippocampal gyrus, ventral striatum, and in the anterior and posterior cingulate gyri. Psychopathic criminals also showed evidence of overactivation in the bilateral fronto-temporal cortex for processing affective stimuli. CONCLUSIONS These data suggest that the affective abnormalities so often observed in psychopathic offenders may be linked to deficient or weakened input from limbic structures.

Neural Pathways Involved in the Processing of Concrete and Abstract Words

The purpose of this study was to delineate the neural pathways involved in processing concrete and abstract words using functional magnetic resonance imaging (fMRI). Word and pseudoword stimuli were presented visually, one at a time, and the participant was required to make a lexical decision. Lexical decision epochs alternated with a resting baseline. In each lexical decision epoch, the stimuli were either concrete words and pseudowords, or abstract words and pseudowords. Behavioral data indicated that, as with previous research, concrete word stimuli were processed more efficiently than abstract word stimuli. Analysis of the fMRI data indicated that processing of word stimuli, compared to the baseline condition, was associated with neural activation in the bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. A direct comparison between the abstract and concrete stimuli epochs yielded a significant area of activation in the right anterior temporal cortex. The results are consistent with recent positron emission tomography work showing right hemisphere activation during processing of abstract representations of language. The results are interpreted as support for a right hemisphere neural pathway in the processing of abstract word representations. Hum. Brain Mapping 7:225–233, 1999.

Temporal lobe abnormalities in semantic processing by criminal psychopaths as revealed by functional magnetic resonance imaging

We tested the hypothesis that psychopathy is associated with abnormalities in semantic processing of linguistic information. Functional magnetic resonance imaging (fMRI) was used to elucidate and characterize the neural architecture underlying lexico-semantic processes in criminal psychopathic individuals and in a group of matched control participants. Participants performed a lexical decision task in which blocks of linguistic stimuli alternated with a resting baseline condition. In each lexical decision block, the stimuli were either concrete words and pseudowords or abstract words and pseudowords. Consistent with our hypothesis, psychopathic individuals, relative to controls, showed poorer behavioral performance for processing abstract words. Analysis of the fMRI data for both groups indicated that processing of word stimuli, compared with the resting baseline condition, was associated with neural activation in bilateral fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior superior temporal gyrus, and left and right inferior frontal gyrus. Analyses confirmed our prediction that psychopathic individuals would fail to show the appropriate neural differentiation between abstract and concrete stimuli in the right anterior temporal gyrus and surrounding cortex. The results are consistent with other studies of semantic processing in psychopathy and support the theory that psychopathy is associated with right hemisphere abnormalities for processing conceptually abstract material.

Pre-exposure of rats to amphetamine sensitizes self-administration of this drug under a progressive ratio schedule

Abstract Two groups of male rats were tested to determine whether pre-exposure to d-amphetamine would enhance the motivation to self-administer the drug under a progressive ratio schedule of reinforcement. In the first phase of the experiment, one group of rats received d-amphetamine (2 mg/kg IP), while a second group received saline on alternate days for a total of ten injections. Following a 21-day drug withdrawal period, behavioral sensitization was confirmed by a significant increase in amphetamine-induced stereotypy in the d-amphetamine-pretreated group, relative to the saline-pretreated group. In the second phase of the study, all rats were implanted with chronic jugular catheters and trained to self-administer d-amphetamine (0.2 mg/kg per infusion) under a fixed-ratio schedule of reinforcement. The progressive ratio paradigm was then imposed for 7 consecutive days; d-amphetamine-pretreated rats attained significantly higher break points than saline-pretreated animals. These data suggest that pre-exposure to d-amphetamine may enhance the motivation to self-administer this drug.

Brain Activity in Cigarette Smokers Performing a Working Memory Task: Effect of Smoking Abstinence

BACKGROUND When nicotine-dependent human subjects abstain from cigarette smoking, they exhibit deficits in working memory. An understanding of the neural substrates of such impairments may help to understand how nicotine affects cognition. Our aim, therefore, was to identify abnormalities in the circuitry that mediates working memory in nicotine-dependent subjects after they initiate abstinence from smoking. METHODS We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study eight smokers while they performed a letter version of the N-Back working memory task under satiety (< or = 1.5 hours abstinence) and abstinence (> or = 14 hours abstinence) conditions. RESULTS Task-related activity in the left dorsal lateral prefrontal cortex (DLPFC) showed a significant interaction between test session (satiety, abstinence) and task load (1-back, 2-back, and 3-back). This interaction reflected the fact that task-related activity in the satiety condition was relatively low during performance of the 1-back task but greater at the more difficult task levels, whereas task-related activity in the abstinence condition was relatively high at the 1-back level and did not increase at the more difficult task levels. CONCLUSIONS We conclude that neural processing related to working memory in the left DLPFC is less efficient during acute abstinence from smoking than at smoking satiety.

Dysfunction of a distributed neural circuitry in schizophrenia patients during a working-memory performance.

BACKGROUND In a recent longitudinal study of first-episode schizophrenia patients, we found that while dysfunction of the right dorsolateral prefrontal cortex (DLPFC), right thalamus, left cerebellum and cingulate gyrus normalized with antipsychotic treatment and significant reduction in symptomatology, the left DLPFC, left thalamus, and right cerebellum remained disturbed. In the present study we investigated whether these abnormalities are also present in clinically stable, relatively well-functioning schizophrenia patients in comparison to control subjects during performance of the N-back working-memory task. METHOD Twelve schizophrenia and 12 control subjects completed the study. The functional images collected during scanning were analyzed using a random-effects model in a restricted set of six regions of interest (ROIs). In addition, the exploratory search in the entire brain volume was performed. RESULTS The ROI analyses revealed relative underactivation in the region of the left DLPFC and the right cerebellum, as well as overactivation in the left cerebellum. The exploratory whole-brain search exposed additional overactivation in the medial frontal, anterior cingulate, and left parietal cortices. CONCLUSIONS The present study provides evidence of significant underactivations in stable schizophrenia patients in regions that we have previously observed to be dysfunctional in acutely psychotic and partially remitted patients, together with extensive overactivations in several regions that potentially reflect some compensatory mechanism or increased effort on the working-memory task.

Effect of Cigarette Smoking on Prefrontal Cortical Function in Nondeprived Smokers Performing the Stroop Task

Some reports indicate that cigarette smoking can help smokers focus attention, even when they have not abstained from smoking for a substantial period of time (eg, >1 h). Understanding the mechanisms by which smoking affects attention may help in designing smoking cessation treatments. Thirteen nonsmokers and nine smokers participated in two tests of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). During fMRI, the participants performed the Stroop Task. There was a 15-min break between the two tests. During the break, each smoker smoked one cigarette. For smokers, the first test began 45–60 min after the last cigarette of ad libitum smoking. The differences in BOLD signal changes between Stroop conditions (ie, incongruent minus congruent) showed a group × test interaction in the right precentral sulcus, including the putative human frontal eye field (FEF). Smokers, but not nonsmokers, showed greater changes (relative to rest) in BOLD signal in the incongruent than in the congruent condition in the first fMRI test but not in the second. Even after brief abstinence from smoking, therefore, smokers exhibit compromised functional efficiency in the right FEF and adjacent precentral sulcus in a test of selective attention; and smoking ameliorates this condition.

Effects of cigarette smoking and abstinence on stroop task performance

RationaleSmokers report enhanced concentration after cigarette smoking and difficulty concentrating when abstinent from smoking. These perceived effects may contribute to smoking cessation failures, and if so, clarification of their cognitive bases could inform treatment strategies. Selective attention may be important in this regard, but earlier literature presents inconsistent findings on how smoking abstinence and resumption of smoking influence this cognitive function.ObjectivesWe aimed to compare smokers and nonsmokers on selective attention, and in smokers, to test the effects of overnight abstinence from smoking and of acute smoking on selective attention.Materials and methodsSmokers and nonsmokers (n = 43) performed a Stroop test (two test days, two test blocks per day). Smokers participated after overnight abstinence and also within 1-h of ad libitum smoking. Smokers each smoked a cigarette between test blocks on each day; nonsmokers did not.ResultsSmokers demonstrated longer response latencies for both congruent and incongruent stimuli after overnight than brief abstinence, but no deficit specifically related to selective attention. Whereas nonsmokers showed no changes in performance in the second test block, smoking between blocks reduced the Stroop effect when smokers were abstinent overnight.ConclusionsThese data are consistent with the hypothesis that abstinence from smoking among nicotine-dependent individuals has deleterious effects on cognitive performance, but do not indicate that selective attention is adversely effected. Improvement in selective attention after terminating abstinence with one cigarette may also contribute to smokers’ perceived enhanced ability to concentrate after smoking.

Sexual dimorphism in schizophrenia: is there a need for gender-based protocols?

Gender differences have been reported in various aspects of schizophrenia, including its epidemiology, clinical course and the response to antipsychotic medications. Over the past few years the authors have been investigating sex differences in brain function in individuals with schizophrenia and have found an intriguing disturbance of normal sexual dimorphism during emotional and cognitive processing. These results can be partly accounted for by altered levels of sex steroid hormones (i.e., estrogen and testosterone) in patients. A handful of clinical research groups have tried low doses of estrogen, testosterone or their precursors as adjunct therapies to the currently available antipsychotic medications in women and men with schizophrenia. The results have been promising, but further investigation is warranted. In the future, new more specific steroidal compounds will be developed and we will see more studies examining sex differences in the brain, behavior and mental health problems. This research will help to identify individuals who may benefit greatest from adjunct hormonal therapies and will further our understanding of the etiology of schizophrenia and other psychiatric disorders.

Disturbed sexual dimorphism of brain activation during mental rotation in schizophrenia.

BACKGROUND Sex differences in visuo-spatial abilities have been well documented in the general population, but there are only a few inconsistent reports in schizophrenia. The purpose of the present study was to examine potential sex differences in performance and pattern of brain activations during mental rotation in schizophrenia patients relative to control participants. METHODS Thirty three schizophrenia patients (17 women and 16 men) were compared to thirty five healthy control participants (17 women and 18 men), while performing a classic mental rotation task (3-D figures). Blood oxygen level dependent (BOLD) echo-planar images were acquired on a 3-Tesla Siemens TRIO system. Random-effect analyses were performed using SPM5 (UK Wellcome Institute). RESULTS Behavioural data revealed a diagnosis-by-sex interaction with healthy men (HM) performing significantly better than schizophrenia men (SZ-M) and no significant difference between healthy women (HW) and schizophrenia women (SZ-W). fMRI results revealed an overall similar pattern of extensive cerebral activations (in the parietal and lateral prefrontal cortex) and deactivations (in the medial prefrontal cortex) in HM and SZ-W during performance of the mental rotation versus control task. In contrast, both HW and SZ-M showed much more restricted activations and no significant deactivations. CONCLUSIONS Sex differences in performance and cerebral activations during mental rotation in schizophrenia patients deviated significantly from what we observed in healthy volunteers. This finding supports and extends existing evidence of a disturbed sexual dimorphism in schizophrenia. Moreover, the results emphasize the importance of including both sexes in neurocognitive and neuroimaging studies of schizophrenia.