Esther Fujiwara

Decision-Making Deficits of Korsakoff Patients in a New Gambling Task With Explicit Rules: Associations With Executive Functions.

Decision-making deficits reflected by risky decisions in gambling tasks have been associated with frontal lobe dysfunctions in various neurologic and psychiatric populations. The question remains whether decision-making impairments are related to executive functions. The authors developed a new gambling task, the Game of Dice Task, with explicit and stable rules for reinforcement and punishment, to investigate relations between executive functions and risk-taking behavior in an explicit decision-making situation. A sample of 35 alcoholic Korsakoff patients and 35 healthy controls was examined with the Game of Dice Task and a neuropsychological test battery. Results show that Korsakoff patients are strongly impaired in this explicit decision-making task and that these disturbances are correlated with specific executive functions.

Decision-making impairments in patients with pathological gambling

Pathological gambling (PG) is most likely associated with functional brain changes as well as neuropsychological and personality alterations. Recent research with the Iowa Gambling Task suggests decision-making impairments in PG. These deficits are usually attributed to disturbances in feedback processing and associated functional alterations of the orbitofrontal cortex. However, previous studies with other clinical populations found relations between executive (dorsolateral prefrontal) functions and decision-making using a task with explicit rules for gains and losses, the Game of Dice Task. In the present study, we assessed 25 male PG patients and 25 male healthy controls with the Game of Dice Task. PG patients showed pronounced deficits in the Game of Dice Task, and the frequency of risky decisions was correlated with executive functions and feedback processing. Therefore, risky decisions of PG patients might be influenced by both dorsolateral prefrontal and orbitofrontal cortex dysfunctions.

No morning cortisol response in patients with severe global amnesia

Activity of the hypothalamus pituitary adrenal (HPA) axis is characterized by a pronounced circadian rhythm. An acute increase in cortisol levels occurs after awakening in the morning with continuously declining levels over the course of the remaining day. The morning cortisol increase probably reflects an activational response of the HPA axis aimed at preparing the body for the day. Some studies found patterns of enhanced or blunted waking cortisol responses observed under chronic stress, burnout, or post traumatic stress disorder. The present study wanted to characterize the morning cortisol response and the circadian cortisol day profile in a sample of six male patients with severe amnesia due to hypoxia, herpes simplex encephalitis or closed head injury. Age and gender matched relatives or friends served as controls. Cortisol was measured from saliva samples collected at home on two consecutive days. The patients were woken up in the morning by their partners or caregivers. The morning cortisol increase typically observed in healthy subjects and also observed in the control group was absent in the amnesic patients. In contrast, a normal circadian day profile was found in the amnesic patients, with a pronounced circadian cortisol decrease. Further studies are needed to understand the neurological or psychological mechanisms leading to a missing morning cortisol response in amnesic patients.

Ventral frontal cortex functions and quantified MRI in traumatic brain injury

Ventral frontal cortex is commonly involved in traumatic brain injury (TBI). The smell identification test (SIT), object alternation (OA), and the Iowa gambling task (IGT) are associated with this brain region in experimental and neuropsychological research. We examined the relationship of performance on these tests to residual structural brain integrity quantified from MRI in 58 TBI patients, including 18 patients with focal cortical contusions and 40 patients with diffuse injury only. Image analysis yielded regional volumetric measures of gray matter, white matter and cerebrospinal fluid. Multivariate analyses identified distributed patterns of regional volume loss associated with test performance across all three behavioral measures. The tasks were sensitive to effects of TBI. In multivariate analyses, performance in all three tasks was related to gray matter loss including ventral frontal cortex, but the SIT was most sensitive to ventral frontal cortex damage, even in patients without focal lesions. The SIT was further related to temporal lobe and posterior cingulate/retrosplenial volumes. OA and the IGT were associated with superior medial frontal volumes. Complex tasks, such as OA and the IGT, do not consistently localize to a single cortical region. The SIT is associated with the integrity of ventral frontal regions, but it is also affected by distributed damage, although the contribution of undetected olfactory tract or bulb damage could not be ruled out. This study illustrates the scope and limitations of functional localization in human ventral frontal cortex.

Functional brain imaging in 14 patients with dissociative amnesia reveals right inferolateral prefrontal hypometabolism

Dissociative amnesia is a condition usually characterized by severely impaired retrograde memory functioning in the absence of structural brain damage. Recent case studies nevertheless found functional brain changes in patients suffering from autobiographical-episodic memory loss in the cause of dissociative amnesia. Functional changes were demonstrated in both resting state and memory retrieval conditions. In addition, some but not all cases also showed other neuropsychological impairments beyond retrograde memory deficits. However, there is no group study available that examined potential functional brain abnormalities and accompanying neuropsychological deteriorations in larger samples of patients with dissociative retrograde amnesia. We report functional imaging and neuropsychological data acquired in 14 patients with dissociative amnesia following stressful or traumatic events. All patients suffered from autobiographical memory loss. In addition, approximately half of the patients had deficits in anterograde memory and executive functioning. Accompanying functional brain changes were measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). Regional glucose utilization of the patients was compared with that of 19 healthy subjects, matched for age and gender. We found significantly decreased glucose utilization in the right inferolateral prefrontal cortex in the patients. Hypometabolism in this brain region, known to be involved in retrieval of autobiographical memories and self-referential processing, may be a functional brain correlate of dissociative amnesia.

Functional retrograde amnesia: A multiple case study

Functional retrograde amnesia (RA) is a rare pathology and has been rarely studied in detail across different patients. We extensively examined five functional RA patients and compared their neuropsychological profile including anterograde and retrograde memory performance, executive functions, emotional processing, and formally assessed psychiatric symptoms. Across patients, neuropsychological deficits beyond RA were most consistently seen in executive functions and attention suggesting that these dysfunctions contribute to the remote memory deficit. In a majority of the patients, problems in social cognition and emotional behaviour were reflected in Theory of Mind deficits and accompanying psychiatric symptoms. Aberrances in a measure of social desirability were detected, pointing to repressive tendencies in three out of the five patients. Future studies of functional RA patients may investigate more specifically which frontal-lobe associated (dys-) functions contribute to the memory retrieval deficit. Moreover, studying more closely the interaction between social cognition, repressive personality style and memory inhibition in this disease seems worthwhile pursuing.

High field structural MRI reveals specific episodic memory correlates in the subfields of the hippocampus

The involvement of the hippocampus (HC) in episodic memory is well accepted; however it is unclear how each subfield within the HC contributes to memory function. Recent magnetic resonance imaging (MRI) studies suggest differential involvement of hippocampal subfields and subregions in episodic memory. However, most structural MRI studies have examined the HC subfields within a single subregion of the HC and used specialised experimental memory paradigms. The purpose of the present study was to determine the association between volumes of HC subfields throughout the entire HC structure and performance on standard neuropsychological memory tests in a young, healthy population. We recruited 34 healthy participants under the age of 50. MRI data was acquired with a fast spin echo (FSE) sequence yielding a 0.52×0.68×1.0 mm(3) native resolution. The HC subfields - the cornu ammonis 1-3 (CA), dentate gyrus (DG), and subiculum (SUB) - were segmented manually within three hippocampal subregions using a previously defined protocol. Participants were administered the Wechsler Memory Scale, 4th edition (WMS-IV) to assess performance in episodic memory using verbal (Logical Memory, LM) and visual (Designs, DE; visual-spatial memory, DE-Spatial; visual-content memory, DE-Content) memory subtests. Working memory subtests (Spatial Addition, SA; and Symbol Span, SSP) were included as well. Working memory was not associated with any HC volumes. Volumes of the DG were correlated with verbal memory (LM) and visual-spatial memory (DE-Spatial). Posterior CA volumes correlated with both visual-spatial and visual-object memory (DE-Spatial, DE-Content). In general, anterior subregion volumes (HC head) correlated with verbal memory, while some anterior and many posterior HC subregion volumes (body and tail) correlated with visual memory scores (DE-Spatial, DE-Content). In addition, while verbal memory showed left-lateralized associations with HC volumes, visual memory was associated with HC volumes bilaterally. This the first study to examine the associations between hippocampal subfield volumes across the entire hippocampal formation with performance in a set of standard memory tasks.

Effects of emotional context on impulse control.

High risk behaviors such as narcotic use or physical fighting can be caused by impulsive decision making in emotionally-charged situations. Improved neuroscientific understanding of how emotional context interacts with the control of impulsive behaviors may lead to advances in public policy and/or treatment approaches for high risk groups, including some high-risk adolescents or adults with poor impulse control. Inferior frontal gyrus (IFG) is an important contributor to response inhibition (behavioral impulse control). IFG also has a role in processing emotional stimuli and regulating emotional responses. The mechanism(s) whereby response inhibition processes interact with emotion processing in IFG are poorly understood. We used 4.7 T fMRI in 20 healthy young adults performing a rapid event-related emotional Go/NoGo task. This task combined the Go/NoGo task, which is a classic means of recruiting response inhibition processes, with emotionally neutral and aversive distractor images. In IFG, both response inhibition in an emotionally neutral context (neutral NoGo trials) and aversive emotional picture processing (aversive Go trials) evoked activation greater than the simple response baseline (neutral Go trials). These results are consistent with the literature. Activation for response inhibition in aversive contexts (aversive NoGo-neutral Go trials) was approximately the sum of response inhibition activation (neutral NoGo-neutral Go) and aversive emotional distractor activation (aversive Go-neutral Go). We conclude that response inhibition and aversive emotional stimulus processing activities combine additively (linearly) in IFG, rather than interfering with each other (sub-linearly) or mutually-enhancing each other (super-linearly). We also found previously undocumented interaction effects between response inhibition (NoGo vs. Go) and emotional context (aversive vs. neutral distractor pictures) in bilateral posterior middle temporal gyrus and angular gyrus, right frontal eye field, and other brain regions. These results may reflect the interaction of attention processes driven by emotional stimuli with conflict resolution processes related to Go/NoGo performance.

Clinical correlates of alexithymia among patients with personality disorder

Abstract The literature portrays patients with alexithymia as unusual and difficult to treat; research to date has not clarified the nature of this condition. This study addressed associations between alexithymia and constructs relevant to clinical intervention, namely attachment, quality of object relations, emotion regulation, defense style, personality disorder, and treatment outcome. Fifty-one patients admitted to an intensive group-oriented day treatment program were recruited. Prior to therapy, patients were administered self-report and structured interview measures of predictor and outcome variables; outcome measures were re-administered at completion of the 18-week program. Alexithymia was common in this sample, with four of five patients endorsing moderate or greater problems. Associations with attachment avoidance, primitive object relations, suppression of emotional expression, use of immature defenses, and severity of borderline personality disorder were identified. Alexithymia did not, however, predict outcome. Findings are considered in terms of how the construct informs views of personality disorder.

Dentate gyrus volume and memory performance in major depressive disorder

BACKGROUND Magnetic resonance imaging (MRI) has shown lower hippocampal volume in major depressive disorder (MDD). Patients with MDD have consistently demonstrated worse performance than healthy controls a number of memory tests. Memory functions within the hippocampus in healthy younger subjects appear to be linked to cornu ammonis (CA1-3) and dentate gyrus (DG) subfields. Therefore, the main goal of the present study was to investigate whether memory deficits in MDD patients are related to reduction in hippocampal subfields volumes, particularly DG and CA 1-3. METHODS 15 MDD patients meeting DSM-IV criteria for MDD with moderate or severe episodes were recruited, together with 15 healthy controls. We used T2-weighted 2D Fast Spin Echo (FSE) and T1-weighted 3D MPRAGE sequences at 4.7 T to compare hippocampal subfield volumes at 0.09 μl voxel volume. Participants were administered the Wechsler Memory Scale. RESULTS MDD patients underperformed in several episodic visual memory tasks, as well as in visual working memory, compared to healthy controls. Global hippocampal volumes were similar between groups; however, MDD patients showed significantly reduced DG volumes within the hippocampal body. Duration of depression correlated with MDD patients׳ total volumes in the hippocampal body and CA1-3 and DG subfields within it. LIMITATIONS Our study sample was relatively small and the majority of patients were on antidepressant treatment. CONCLUSIONS Our findings suggest that DG volumes in particular may be worthy of further study to further elucidate their precise role in MDD, both by itself as well as in relation to memory.