Selective delayed alternation deficits in dominantly inherited olivopontocerebellar atrophy

In order to characterize more completely the nature of the frontal lobe-type cognitive changes in patients with dominantly inherited olivopontocerebellar atrophy (OPCA) we administered two tasks sensitive to frontal system dysfunction, delayed alternation (DA) and delayed response (DR), to 12 patients from one OPCA family. Affected members from this family have previously been shown to have a marked and widespread cerebral (including frontal) cortical cholinergic reduction as severe as that observed in Alzheimer's disease. Performance on DA, but not on DR, was significantly impaired in the OPCA patients compared to that in the controls. We suggest that the DA deficits in OPCA could be a consequence of a loss of cholinergic innervation to orbitofrontal or possibly temporal cortical areas and/or damage to the integrity of the cerebello-frontal neuronal connections.     

Spatial learning on the Morris Water Maze Test after a short-term paradoxical sleep deprivation in the rat

Twelve rats were deprived of paradoxical sleep (PS) for eight hours using the small platform method. PS-deprived and control rats then learned either the standard allocentric version (using external cues) of the Morris Water Maze (MWM) or a delayed alternation version (changing the platform location between trials: MWM(DA)). Overall, rats learning the MWM(DA) made more quadrant entries than rats learning the allocentric version. Compared to other rats, PS-deprived rats crossed more quadrants only in the MWM(DA). These results show that MWM(DA) is a more complex task to learn and is more vulnerable to PS deprivation than allocentric spatial orientation. Since delayed alternation is dependent upon frontal structures, we propose that tasks involving the frontal cortex are more sensitive to short-term PS deprivation than tasks related to hippocampal structures.     

Frontal brain asymmetry in depression with comorbid anxiety: a neuropsychological investigation

The approach-withdrawal model posits that depression and anxiety are associated with a relative right asymmetry in frontal brain activity. Most studies have tested this model using measures of cortical brain activity such as electroencephalography. However, neuropsychological tasks that differentially use left versus right frontal cortical regions can also be used to test hypotheses from the model. In two independent samples (Study 1 and 2), the present study investigated the performance of currently depressed individuals with or without a comorbid anxiety disorder and healthy controls on neuropsychological tasks tapping primarily left (verbal fluency) or right (design fluency) frontal brain regions. Across both samples, results indicated that comorbid participants performed more poorly than depressed only and control participants on design fluency, while all groups showed equivalent performance on verbal fluency. Moreover, comorbid participants showed "asymmetrical" performance on these two tasks (i.e., poorer design [right frontal] relative to verbal [left frontal] fluency), whereas depressed only and control participants showed approximately symmetrical profiles of performance. Results from these two samples suggest an abnormal frontal asymmetry in neurocognitive performance driven primarily by right frontal dysfunction among anxious-depressed individuals and highlight the importance of considering comorbid anxiety when examining frontal brain functioning in depression.     

Role of dopamine,the frontal cortex and memory circuits in drug addiction: insight from imaging studies

Drug addiction is characterized by a set of recurring processes (intoxication, withdrawal, craving) that lead to the relapsing nature of the disorder. We have used positron emission tomography to investigate in humans the role of dopamine (DA) and the brain circuits it regulates in these processes. We have shown that increases in DA are associated with the subjective reports of drug reinforcement corroborating the relevance of drug-induced DA increases in the rewarding effects of drugs in humans. During withdrawal we have shown in drug abusers significant reductions in DA D2 receptors and in DA release. We postulate that this hypodopaminergic state would result in a decreased sensitivity to natural reinforcers perpetuating the use of the drug as a means to compensate for this deficit and contributing to the anhedonia and dysphoria seen during withdrawal. Because the D2 reductions are associated with decreased activity in the anterior cingulate gyrus and in the orbitofrontal cortex we postulate that this is one of the mechanisms by which DA disruption leads to compulsive drug administration and the lack of control over drug intake in the drug-addicted individual. This is supported by studies showing that during craving these frontal regions become hyperactive in proportion to the intensity of the craving. Craving is also associated with activation of memory circuits including the amygdala (implicated in conditioned learning), hippocampus (implicated in declarative learning), and dorsal striatum (implicated in habit learning) all of which receive DA innervation. We therefore postulate that dopamine contributes to addiction by disrupting the frontal cortical circuits that regulate motivation, drive, and self-control and by memory circuits that increase the motivational salience of the drug and drug-associated stimuli.     

Cognitive Components in Perseverative and Nonperseverative Errors on the Object Alternation Task

Knowledge of response rules in the object alternation (OA) task was experimentally manipulated in 20 alcohol-dependent men and 20 controls. The results suggest that perseverative and nonperseverative errors in OA are under the direct control of task-specific knowledge which must be induced and retained from trial to trial, and that impaired response inhibition is not solely responsible for poor performance on these tasks. The demonstration of a cognitive contribution to poor performance on the OA task suggests that rule induction must be achieved before successful response selection and inhibition can take place. We conclude by discussing implications for our understanding of other delayed response tasks and clinical tests of prefrontal function (e.g., the Wisconsin Card Sorting Test (WCST) and the Halstead Category Test).     

Object alternation and orbitofrontal system dysfunction in Alzheimer's and Parkinson's disease

Previous performance on measures of frontal system function have suggested prominent orbitofrontal system damage in Alzheimer's disease, but not in Parkinson's dementia. Object alternation (OA), a task sensitive to orbitofrontal system dysfunction in non-human animals, was therefore administered to determine whether this measure would distinguish Alzheimer's from Parkinson's dementia. OA was significantly impaired in Alzheimer's disease compared to Parkinson's dementia, even though both groups were equated for severity of dementia. Although the patients with Parkinson's dementia also showed impairment on OA compared to normals, an error analysis revealed that the performance of the Alzheimer's patients, but not the Parkinson's patients, was characterized by abnormal response perseveration. The marked perseverative deficit in Alzheimer's disease may reflect orbitofrontal system dysfunction whereas the milder, and qualitatively different, deficits in Parkinson's disease may reflect dorsolateral frontal system involvement.     

A twin study of spatial and non-spatial delayed response performance in middle age

Delayed alternation and object alternation are classic spatial and non-spatial delayed response tasks. We tested 632 middle-aged male veteran twins on variants of these tasks in order to compare test difficulty, measure their inter-correlation, test order effects, and estimate heritabilities (proportion of observed variance due to genetic influences). Non-spatial alternation (NSA), which may involve greater reliance on processing of subgoals, was significantly more difficult than spatial alternation (SA). Despite their similarities, NSA and SA scores were uncorrelated. NSA performance was worse when administered second; there was no SA order effect. NSA scores were modestly heritable (h(2)=.25; 26); SA was not. There was shared genetic variance between NSA scores and general intellectual ability (r(g)=.55; .67), but this also suggests genetic influences specific to NSA. Compared with findings from small, selected control samples, high "failure" rates in this community-based sample raise concerns about interpretation of brain dysfunction in elderly or patient samples.     

A thematic analysis of practitioners' understanding of domestic abuse in terms of post‐traumatic stress disorder (PTSD) and complex‐PTSD (C‐PTSD)

There is a growing body of evidence suggesting that domestic abuse (DA) should be conceptualised within the complex post‐traumatic stress disorder (C‐PTSD) model. Recently, in the draft of the International Classification of Diseases, Eleventh Revision, produced by the World Health Organization (WHO), C‐PTSD was included as a separate criterion in which DA is incorporated (ICD‐11, WHO, 2018). In this study, a thematic analysis was used to explore to what extent practitioners working with DA survivors are familiar with PTSD and C‐PTSD. Research into such a prevalent and detrimental problem as DA is important to understand whether the development of theoretical knowledge about DA and C‐PTSD is addressed in practice. In a Women's Centre in South London, six semi‐structured interviews with middle‐aged female practitioners were conducted to investigate each counsellor's experiences, knowledge and reflections. Six final themes were constructed to summarise the main results. The findings demonstrate limited practitioner understanding of DA in terms of C‐PTSD, which seems to impact not only the effectiveness of treatment plans with DA survivors, but also counsellors’ own psychological and physical states. It is also indicated that DA can be conceptualised within the C‐PTSD model that corresponds with previous literature indicating the complex nature of DA. The overall results of the current research acknowledge that DA sectors should not be neglected and better funding and effective psychoeducation in this field are needed.     

PTSD arousal and depression symptoms associated with increased right-sided parietal EEG asymmetry

Researchers have proposed that depression and particular types of anxiety are associated with unique patterns of regional brain activation. The authors examined the relationship among posttraumatic stress disorder (PTSD), anxiety, and depressive symptoms and frontal, temporal, and parietal EEG alpha asymmetry in female Vietnam War nurse veterans. The results indicate that PTSD arousal symptoms are associated with increased right-sided parietal activation. However, the combination of arousal, depression, and their interaction explain more than twice the variance in parietal asymmetry compared with arousal alone. The results support the contention that the association between anxiety and right-sided posterior activation is specific to the anxious arousal subtype. These findings underscore the importance of isolating, both theoretically and statistically, emotional subcomponents in studies of regional brain activation.     

Physiological arousal and attention in veterans with posttraumatic stress disorder

Psychophysiological reactivity has been well documented in WWII, Korean Conflict, and Vietnam veterans with posttraumatic stress disorder (PTSD). In addition, these individuals have demonstrated cognitive impairments within the domains of attention, concentration, new learning, and memory. However, there has been no research examining the impact of physiological arousal on attention in individuals with PTSD. This study documents the level of physiological arousal and associated disruption of attentional abilities in 28 Persian Gulf War veterans (18 without PTSD or other psychopathology and 10 with PTSD). This population represents a group of combat trauma victims who experienced a relatively acute onset of PTSD, thus providing a unique opportunity to compare prior psychophysiological and cognitive results with a group of veterans who manifested a recent onset of PTSD. Results indicated relatively comparable psychophysiological reactivity and arousal between Persian Gulf War veterans with PTSD and Persian Gulf War veterans without PTSD. Furthermore, attentional processes of veterans with PTSD were not more disrupted than in comparison soldiers. Results suggest that the intensity and chronicity of the disorder may impact physiological arousal and disruption of cognitive functioning. Following Persian Gulf War veterans with PTSD over time may reveal that psychophysiological arousal becomes more pronounced with chronicity, perhaps as memory networks become strengthened and/or neuroendocrine systems become increasingly disrupted.     

The role of the glutamatergic system in posttraumatic stress disorder

Antiglutamatergic agents, such as lamotrigine, have been used successfully for the treatment of posttraumatic stress disorder (PTSD). They could be potentially acting through the stabilization of the corticotropin-releasing factor (CRF) systems. Glutamate mediates CRF release in various brain regions involved in the pathophysiology of PTSD, antiglutamatergic agents could stabilize the CRF system and, thereby, improve the symptom complex of PTSD (reexperiencing, hyperarousal, and avoidance). The role of glutamate and CRF in PTSD and other anxiety disorders are still being elucidated. However, it is clear that the glutamatergic systems play a role in the pathophysiology of PTSD.     

Inter-brain co-activations during mindfulness meditation. Implications for devotional and clinical settings

Mindfulness meditation usually takes place as personal, introspective activity. It is not known if this practice activates the brain differently when done alone or with someone else.Sixteen couples of expert meditators performed mindfulness-oriented meditation (MOM) and instructed mind-wandering (IMW) tasks in two conditions: once sitting in the same room (SR) and once in two different rooms (DR). Spontaneous electroencephalographic (EEG) data was collected during 7-minute recording sessions in the four experimental settings (MOM/SR, MOM/DR, IMW/SR, IMW/DR). Power in band was computed in separate clusters of independent components of the EEG signals.In addition to significant task effects, found in frontolimbic (MOM > IMW in gamma) and frontoparietal locations (MOM < IMW in theta), significant condition effects were found in frontal (SR > DR in delta) and in temporo-occipital regions (SR > DR in theta and alpha). Moreover, a significant interaction between task and condition revealed higher gamma activity in limbic areas during MOM/SR vs. MOM/DR settings. This effect was not attributable to gender, age nor the meditation expertise of participants.We thus show that the brains of two people work differently when they are doing something together or alone; some of these differences are specific to mindfulness meditation. Implications for devotional and clinical settings are discussed.     

Regional brain electrical activity in posttraumatic stress disorder after motor vehicle accident

This study examined whether patients with posttraumatic stress disorder (PTSD) related to motor vehicle accidents (MVAs) would show an abnormal pattern of electroencephalographic (EEG) alpha asymmetries, which has been proposed for particular types of anxiety. Patients with PTSD (n = 22) or subsyndromal PTSD (n = 21), traumatized controls without PTSD (non-PTSD with MVA; n = 21), and healthy controls without MVA (n = 23) underwent measurement of EEG activity during baseline and exposure to a neutral, a positive, a negative, and an accident-related picture. Differences in brain asymmetry between groups were observed only during exposure to trauma-related material. PTSD and subsyndromal PTSD patients showed a pattern of enhanced right anterior and posterior activation, whereas non-PTSD with MVA participants showed the opposite pattern. Furthermore, posterior asymmetry in nontraumatized healthy controls varied with gender, with female participants showing a pattern of higher right posterior activation. The results support the hypothesis that symptomatic MVA survivors are characterized by a pattern of right hemisphere activation that is associated with anxious arousal and symptoms of PTSD during processing of trauma-specific information.     

Brain-imaging studies of posttraumatic stress disorder

Brain-imaging studies of posttraumatic stress disorder (PTSD) have rapidly increased in recent years. Structural studies have identified potential smaller volumes of the hippocampus of traumatized and/or PTSD subjects. Functional activation studies have implicated hyperactive or altered functioning of brain regions, such as the amygdala and the insula, and a failure to engage emotional regulatory structures, such as the medial prefrontal and anterior cingulate cortex. Recent neurochemical investigations have suggested that neuromodulatory systems (eg, gamma-aminobutyric acid, micro-opioid) may underlie these aberrant brain activation patterns. This article reviews the literature on structural, functional, and neurochemical brain-imaging studies of PTSD.     

Seeking the source of emotional Stroop interference effects in PTSD: A study of P3s to traumatic words

We investigated the source of emotional Stroop interference effects in posttraumatic stress disorder (PTSD) by measuring reaction times and P3 latencies and amplitudes to personal traumatic, personal positive, and neutral words in a modified Stroop paradigm. Individuals with PTSD were slower to indicate word color, especially for traumatic words, thereby replicating emotional Stroop interference in PTSD. Individuals with PTSD also had significantly reduced and delayed P3 components across word types. Across diagnostic groups, frontal P3 amplitudes were larger to personal positive and traumatic words compared to standard neutral words. However, the absence of Diagnosis x Word Type interactions for P3 measures suggests that individuals with PTSD do not differ from individuals without PTSD in the encoding and recognition of the color of traumatic relative to nontraumatic words, and that Stroop interference does not occur during these early stages of processing.     

Autobiographical memory in posttraumatic stress disorder before and after treatment

Although overgeneral retrieval of autobiographical memories has been repeatedly demonstrated in posttraumatic stress disorder (PTSD), no studies have indexed overgeneral retrieval before and after treatment of PTSD. Autobiographical memory was assessed in PTSD participants (n=20) prior to commencing cognitive behaviour therapy and 6 months after therapy completion. Fifteen participants completed both assessments. Improvement in PTSD symptoms was significantly associated with improved retrieval of specific memories and decreased retrieval of categoric memories in response to positive cues. These data suggest that symptom reduction during treatment of PTSD leads to greater access to specific memories of positive experiences.     

Sleep disturbances in the aftermath of trauma and posttraumatic stress disorder

Sleep disturbances, including nightmares and insomnia, are prominent following trauma and with posttraumatic stress disorder (PTSD) and likely contribute to the pathogenesis of the disorder. Findings from laboratory studies of PTSD have been inconsistent in terms of documenting objective impaired sleep maintenance but have been somewhat more consistent in indicating alterations of rapid eye movement (REM) sleep. Studies of the early aftermath of trauma can reduce the complexity associated with chronicity and comorbidity, and may have implications for early diagnosis and prevention. Multiple studies indicate that dream content is affected by recent threatening experiences. The development of PTSD is associated with a more replicative type of nightmare content. Sleep is reported to be generally disrupted following trauma especially among those developing PTSD. The limited number of studies that provide objective recorded indices during the early aftermath of trauma also provide a mixed picture regarding overall sleep maintenance. Recent data suggest that a more specific disruption of REM sleep may be associated with the development of PTSD and that this disruption is associated with an increased signal of sympathetic nervous system activation during REM sleep. Disrupted REM sleep and increased sympathetic/noradrenergic activity may have implications for understanding recent promising interventions for PTSD sleep disturbance that can be applied to early intervention.     

Anxiety buffer disruption theory: a terror management account of posttraumatic stress disorder

We present anxiety buffer disruption theory (ABDT) and provide a review of current evidence regarding the theory. ABDT is an application of terror management theory to explain diverse reactions to traumatic events and the onset and maintenance of posttraumatic stress disorder (PTSD). It posits that PTSD results from a disruption in one's anxiety-buffering mechanisms, which normally provide protection against anxiety in general and death anxiety in particular. The disruption of these mechanisms leaves the individual defenseless in the face of overwhelming anxiety, which leads to the major symptom clusters of PTSD: re-experiencing, hyper-arousal, and avoidance. According to ABDT, because of the disruption in their anxiety-buffering mechanisms, individuals with PTSD symptoms do not respond to mortality reminders in the defensive ways that psychologically healthier individuals do. We review four sets of studies conducted in four different cultures and with people who have experienced different types of trauma, which reveal this atypical response pattern and lend support to ABDT.     

Acquisition and maintenance of delayed matching-to-sample in tufted capuchin monkeys

Delayed matching-to-sample (DMTS) is a commonly used procedure to investigate short-term memory. For the study of functions of forgetting, the delay between the disappearance of the sample stimulus and appearance of choices is manipulated. The intertrial interval (ITI) is also varied to assess interference effects. Performance decrements have been observed as delay increases and, in some cases, performance recovery occurs when ITIs are increased. Other studies indicate that the higher the ITI/delay ratio, the greater the accuracy in DMTS. In this study, 2 experiments investigated DMTS performances of 3 tufted capuchin monkeys as function of delay and ITI. In Experiment 1, alternation of gradual increases of delay and ITI was effective in producing ≥90% accuracy at delays as long as 90 s. Individual monkeys differed in the highest value of delay at which this criterion was met. In Experiment 2, the monkeys were exposed to 5-s DMTS with different ITIs to assess the effects of various ITI/delay ratios on accuracy. Highest accuracy tended to occur at the higher ITI/delay ratios.