A neuropsychological investigation of prefrontal cortex involvement in acute mania

OBJECTIVE: Mania has received little attention from a contemporary neuropsychological perspective despite its clear resemblance to the disinhibition syndrome sometimes seen after frontal brain injury, particularly injury to the inferior aspect of the prefrontal cortex. The purpose of this investigation was to describe the neuropsychological profile of severe acute mania by using a range of tasks selected primarily for the detection of localized neural disruption within the prefrontal cortex. METHOD: Fifteen acutely manic inpatients were compared with 30 nonpsychiatric subjects on tasks from the Cambridge Automated Neuropsychological Test Battery (Tower of London, spatial working memory, intradimensional-extradimensional attentional shift, and rapid visual information processing tasks) and on the Iowa Gambling Task, Stroop Color and Word Test, a verbal fluency task, and the California Verbal Learning Test. RESULTS: Discriminant function analysis identified deficits in sustained attention (on the rapid visual information processing task) and verbal learning (on the California Verbal Learning Test) as the best indicators of manic performance, rather than deficits on any of the tests of executive functioning. The model correctly classified 91% of subjects overall and 87% of manic subjects. Manic patients did not resemble patients with ventromedial prefrontal cortex damage in their performance on the Iowa Gambling Task. CONCLUSIONS: Acute mania is characterized by core deficits in verbal memory and sustained attention against a background of milder impairments in functions that are traditional measures of prefrontal cortex integrity (attentional set shifting, planning, working memory). The data do not implicate ventral prefrontal cortex disruption as a locus of pathology in acute mania. Verbal memory and sustained attention deficits may relate differentially to the state and trait characteristics of bipolar disorder.     

Declarative memory and WCST-64 performance in subjects with schizophrenia and healthy controls

The Wisconsin Card Sorting Test (WCST) is a set-switching task used extensively to study impaired executive functioning in schizophrenia. Declarative memory deficits have also been associated with schizophrenia and may affect WCST performance because continued correct responding depends on remembering the outcome of previous responses. This study examined whether performance in visual and verbal declarative memory tasks were associated with WCST performance. Subjects comprised 30 patients with schizophrenia or schizoaffective disorder (SCZ) and 30 demographically matched healthy controls (CON) who were tested on the WCST, the Benton Visual Retention Test (BVRT), the California Verbal Learning Test (CVLT), and the Continuous Performance Test (CPT). SCZ subjects showed significant correlations between visual and verbal declarative memory and performance on the WCST-64 that were in the hypothesized direction such that worse memory performance was associated with worse performance on the WCST. CON subjects did not show a significant relationship between visual or verbal memory and WCST-64 performance. Fisher's r to z transformations indicated that the associations between declarative memory and WCST-64 performance in the SCZ subjects differed significantly from those of CON subjects. The findings suggest that interpretations of WCST-64 scores for subjects with schizophrenia should be considered in light of their declarative memory functioning.     

The Role of Depression in Verbal Memory Following Traumatic Brain Injury

The purpose of this study was to characterize the relationship between verbal memory and depression scores on the Personality Assessment Inventory following traumatic brain injury. Depression was associated with diminished delayed recall and recognition on the California Verbal Learning Test-II (CVLT-II), even after controlling for a neuropsychological composite score and/or a measure of motivation (i.e., the TOMM). There was no relationship between depression and recall on Verbal Paired Associates or Logical Memory when controlling for the same covariates. The findings were most consistent with depressed subjects failing to utilize the semantic organization of the CVLT-II list to enhance their learning.     

The role of depression in verbal memory following traumatic brain injury

The purpose of this study was to characterize the relationship between verbal memory and depression scores on the Personality Assessment Inventory following traumatic brain injury. Depression was associated with diminished delayed recall and recognition on the California Verbal Learning Test-II (CVLT-II), even after controlling for a neuropsychological composite score and/or a measure of motivation (i.e., the TOMM). There was no relationship between depression and recall on Verbal Paired Associates or Logical Memory when controlling for the same covariates. The findings were most consistent with depressed subjects failing to utilize the semantic organization of the CVLT-II list to enhance their learning.     

Discrepancies between the California Verbal Learning Test: Children's Version and the Children's Category Test after pediatric traumatic brain injury.

One hundred 9-16-year-old children with traumatic brain injury (TBI) completed the California Verbal Learning Test-Children's Version (CVLT-C) and the Children's Category Test (CCT) within 1 year after injury. Performance contrasts between these two instruments that were unusually large (> 16 T score points) were about as common in this clinical sample as in the standardization sample of both instruments. However, relatively poor performance on the CVLT-C as compared to the CCT was associated with prolonged coma and lower scores on the Processing Speed index of the Wechsler Intelligence Scale for Children-Third Edition. It is concluded that a relative weakness on the CVLT-C is more likely to reflect cerebral compromise after pediatric TBI than is a relative weakness on the CCT.     

Memory performance on the California Verbal Learning Test-II: findings from patients with focal frontal lesions.

Numerous studies have suggested that frontal cortex plays a strategic, rather than an absolute, role in memory performance. Typically, frontal patients are reported to have impaired recall but normal recognition memory. A recent meta-analysis, however, has questioned this conclusion. To further investigate the role of frontal cortex in long-term memory, patients with focal frontal lesions and age- and education-matched controls were tested on a new version of the California Verbal Learning Test (CVLT-II). Frontal patients exhibited a number of deficits on this test, including overall poorer recall, an increased tendency to make intrusions, reduced semantic clustering, and impaired yes/no recognition performance. Further analysis of the error rates in the yes/no recognition task revealed that frontal patients were most likely to mistakenly endorse 2 types of distractors: semantically related words and words from an interference list. These findings are discussed with respect to the role of frontal dysfunction in false recollections and poor source memory, as well as the distinction between the roles of frontal and temporal cortex in long-term memory.     

Verbal learning and memory after childhood stroke.

Verbal learning and memory (VLM) following pediatric stroke was characterized in a cross-sectional neuropsychological and neuroimaging study of 26 subjects, aged 5 to 17, with a history of pediatric stroke and 26 age, SES, and gender matched orthopedic controls. Further comparisons were made between the VLM profiles of stroke subjects with right versus left hemisphere lesions and early (> 12 months) versus late (12 months) strokes. Overall, stroke subjects scored significantly lower than control subjects on several VLM indices (California Verbal Learning Test-Children; CVLT-C), as well as on measures of intellectual functioning (IQ) and auditory attention/working memory (Digit Span). Subgroup analyses of the stroke population found no significant differences in VLM, Digit Span, Verbal IQ or Performance IQ when left-hemisphere lesion subjects were compared to right-hemisphere lesion subjects. In contrast, early strokes were associated with significantly fewer words recalled after delay, reduced discriminability (fewer correct hits relative to false positive errors on recognition testing), and relatively worse auditory attention/working memory scores (Digit Span). These findings indicate that pediatric stroke subjects demonstrated more VLM impairment than control subjects, and early strokes were associated with greater recall and recognition deficits. In stark contrast with adult-onset stroke, both left- and right-hemisphere lesions during childhood resulted in similar VLM performance.     

Ictal mnemestic aura and verbal memory function

Déjà vu aura is a well-known phenomenon experienced by some patients with epilepsy. This study sought to explore the relationship between verbal memory and the experience of déjà vu or other types of mnemestic auras in 42 individuals with intractable seizures and 42 age- and education-matched patient controls. Verbal memory was assessed with indices of learning, long delay recall, and recognition from the California Verbal Learning Test. Results indicated that auras of any type were not associated with memory performance on the California Verbal Learning Test. As expected, age and education were related to verbal memory performance. Mnemestic auras were associated with clinical indices of illness, suggesting that the presence of these auras may be regarded as a risk factor for greater chronicity and severity in epilepsy.     

A comparison of memory for verbal and non-verbal material in schizophrenia

Verbal memory impairment has been well explored in schizophrenia, but it is unclear whether findings relate to the type of material to be learned or the component process required by the memory task. Also, sparse data on non-verbal memory also open the question of how well schizophrenia patients encode this material. We tested whether episodic memory performance in schizophrenia varies as a function of stimulus material (verbal/non-verbal) and determined the integrity of various component memory processes. Memory tests that differ in stimulus material (words, California Verbal Learning Test, CVLT; designs, Biber Figure Learning Test-Extended, BFLT-E) yet produce similar memory component measures were used. Subjects were 28 neuroleptic-medicated inpatients with a diagnosis of chronic schizophrenia. Results showed that both verbal and non-verbal memory performance was impaired relative to age-matched controls. Learning and recall measures were most severely impaired, with memory storage problems and impairment in recognition memory evident. On the verbal task, the relative sparing of recognition memory suggested retrieval processes, in addition to encoding processes, were disrupted. On the non-verbal task, the deficits appeared more limited to encoding. Therefore, while the operational integrity of components such as encoding were compromised regardless of material, retrieval processes showed material-specific effects. To the degree verbal and non-verbal memory functions can be lateralized in the brain, these data support the possibility of deficits in both right and left hemisphere declarative memory systems in schizophrenia.     

No effect of PTSD and other psychiatric disorders on cognitive functioning in veterans with mild TBI

There has been speculation that post-traumatic stress disorder (PTSD) superimposed on mild traumatic brain injury (mTBI) may have synergistic, negative effects on cognitive functioning. The purpose of this study was to investigate differences in processing speed, executive functioning, and memory of 82 veterans with mTBI and PTSD, mTBI, and another psychiatric condition, or mTBI alone. It was hypothesized that there would be no group differences in cognitive performances. Participants completed the Trail Making Test, Stroop, Rey Complex Figure, and California Verbal Learning Test-2. There were no significant group differences on any cognitive measure. Findings suggest that PTSD and other psychiatric disorders do not necessarily have a negative exacerbating effect on processing speed, executive functioning, or memory in veterans with mTBI.     

Verbal learning subtypes in traumatic brain injury: A replication

Abstract

Traumatic brain injury (TBI) has been associated with memory impairments, but the severity and qualitative aspects of such impairment do not appear homogeneous across patients. This study sought to replicate an earlier investigation that found distinct verbal learning subtypes in TBI using the California Verbal Learning Test (CVLT). CVLT data from 88 acute rehabilitation inpatients with mild, moderate, and severe traumatic brain injuries were analyzed with multiple cluster analytic techniques. Cluster analyses yielded five learning subtypes, three of which appeared similar to the subtypes previously identified as Active. Disorganized, and Passive subtypes, and two that appeared similar to the Deficient subgroup. Traumatic brain injury appears to be characterized by heterogeneous, but fairly reliable, verbal learning subtypes that can be detected early postinjury.     

Encoding and recognition after traumatic brain injury: neuropsychological and functional magnetic resonance imaging findings

Although impairment of episodic memory is common after traumatic brain injury (TBI), the complex nature of human memory suggests the need to study more than recall alone. For this reason, we are presenting an extension with additional analyses of persons reported in a previous publication ( Russell, Arenth, Scanlon, Kessler, & Ricker, 2011 ). We examined both the encoding and recognition components of an episodic memory paradigm containing both word and letter string blocks using functional magnetic resonance imaging (fMRI) and neuropsychological testing. This paradigm was completed by 12 persons with complicated mild, moderate, or severe TBI and 12 matched uninjured controls. Comparisons were made between groups and stimulus types. While task behavioral performance was not significantly different between groups, imaging results showed greater activation for the TBI group during the encoding portion of the task, while the control group exhibited more activation on the recognition portion. Observed areas of activation suggest that the TBI group may have used a less effective, but more automatic verbal strategy for encoding the nonpronounceable letter strings, while controls may have opted for more of a recognition-focused strategy. Group differences in California Verbal Learning Test-Second Edition (CVLT-II) performance supported these ideas, and further neuropsychological testing also suggested limitations in executive functioning in the TBI group that may have influenced performance. Implications for intervention are discussed.     

Performance on the California Verbal Learning Test After Traumatic Brain Injury

The California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, & Ober, 1987) data of 150 patients with traumatic brain injury (TBI) were evaluated to determine the latent underlying constructs as well as the possibility of performance subtypes with criterion validity. Confirmatory factor analysis of eight competing latent variable models suggested that a four-factor model (composed of Attention Span, Learning Efficiency, Delayed Recall, and Inaccurate Recall) fit the data relatively well. Two-stage cluster analysis of marker variables of each of these four factors suggested the presence of four reliable subtypes. Level of performance differences between these clusters were related to injury severity parameters. It is concluded that the CVLT is a sensitive and mulitfactorial measure of learning and memory after TBI. Specific recommendations for interpretation of clinically obtained CVLT profiles are provided.     

Performance on the California Verbal Learning Test after traumatic brain injury.

The California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, & Ober, 1987) data of 150 patients with traumatic brain injury (TBI) were evaluated to determine the latent underlying constructs as well as the possibility of performance subtypes with criterion validity. Confirmatory factor analysis of eight competing latent variable models suggested that a four-factor model (composed of Attention Span, Learning Efficiency, Delayed Recall, and Inaccurate Recall) fit the data relatively well. Two-stage cluster analysis of marker variables of each of these four factors suggested the presence of four reliable subtypes. Level of performance differences between these clusters were related to injury severity parameters. It is concluded that the CVLT is a sensitive and mulitfactorial measure of learning and memory after TBI. Specific recommendations for interpretation of clinically obtained CVLT profiles are provided.     

Independent effects of tobacco abstinence and bupropion on cognitive function in schizophrenia

OBJECTIVE: The objective of this study was to examine the effects of tobacco abstinence and bupropion treatment on cognitive functioning in adult smokers with schizophrenia in the setting of a randomized, double-blind, placebo-controlled clinical trial of bupropion for smoking cessation. METHOD: Fifty-three adults with schizophrenia (DSM-IV) took part in a trial of bupropion for smoking cessation. Subjects were enrolled in the study from August 1999 to March 2003. Forty-five subjects remained in the trial at week 4; 41 subjects, 19 taking bupropion and 22 taking placebo, completed the baseline and week 4 cognitive assessments and were included in the analysis of adjusted effects of abstinence and bupropion treatment on cognitive function. RESULTS: Controlling for bupropion treatment and baseline performance, 7 days of tobacco abstinence was associated with slowed motor speed (finger tapping) but was not associated with worsening of performance on tests of attention (AX Continuous Performance Test [AX-CPT]), verbal learning and memory (California Verbal Learning Test [CVLT]), working memory (digit span), or executive function/inhibition (Stroop) and was not associated with worsening of any clinical measures. Controlling for abstinence status, bupropion was associated with reduction (improvement) in reaction time variability on the AX-CPT and with reduction in perseverative errors on the CVLT. CONCLUSION: We conclude that 1 week of tobacco abstinence is associated with slowed motor speed but is not associated with detectable worsening in performance on a range of neuropsychological tests or clinical symptoms in the subset of patients who were able to quit smoking. We also conclude that bupropion treatment may be associated with improvement in variability of attention.     

Motivation and Neuropsychological Test Performance Following Mild Head Injury

Effect of motivation on neuropsychological test performance in mild head injury was assessed. Motivation was measured using the Portland Digit Recognition Test. Three groups were compared: (a) mild head injury, financial incentives, good motivation; (b) mild head injury, financial incentives, poor motivation; (c) moderate/severe head injury, good motivation. The neuropsychological battery included measures of sensory function, motor function, attention, intelligence, reasoning, and memory. Mild head injury well motivated patients performed significantly better than the other two groups on some tests. Mild head injury poorly motivated individuals and moderate-severe head injury patients were indistinguishable on many tests. Consistent with previous reports, tactile sensory (finger recognition and Fingertip Number Writing Perception) and recognition memory (Rey Auditory Verbal Learning) tasks were identified as clinically useful measures of poor motivation. On these measures mild head injury well motivated examinees performed no better than moderate-severe patients, with both groups superior to mild head injury poorly motivated examinees. Sensitivity and specificity data are reported. Our measures of tactile sensation and verbal recognition memory were more affected by motivation than by the severity of head injury.     

Declarative and procedural memory in bipolar disorder.

BACKGROUND: Memory function is an important but under researched area for neuropsychological investigation in persons with bipolar disorder. Previous studies have reported cognitive deficits on tasks of declarative memory in bipolar patients in the euthymic state. METHODS: This study extended these findings by investigating declarative as well as procedural learning and memory in bipolar patients (with and without alcohol abuse) who were examined in the euthymic state. The California Verbal Learning Test, Star Mirror Tracing Task, Pursuit Rotor Task, American National Adult Reading Test, and the Vocabulary Subtest of the WAIS-R, were administered to bipolar patients and control subjects by researchers who were blind to the subject's group. RESULTS: Bipolar patients performed worse than control subjects on a measure of declarative memory (California Verbal Learning Test) but did not differ from the performance of control subjects on either of the two procedural learning tasks (Pursuit Rotor Task and Star Mirror Task). CONCLUSIONS: These results suggest disturbed function of temporal lobe, but not basal ganglia, structures in persons with bipolar disorder.     

Verbal memory in mania: effects of clinical state and task requirements

Objectives: Manic patients exhibit impaired verbal learning and memory, particularly following longstanding illness. However, it is unclear whether recognition and recall performance are differentially influenced by a manic mood state.
Methods: To examine this issue, we administered the California Verbal Learning Test and symptom-rating scales to inpatients with pure or mixed mania, euthymic outpatients, and healthy comparison subjects.
Results: An overall performance difference was identified between groups. Manic and euthymic patients performed more poorly than healthy subjects on recall. However, manic patients performed more poorly than euthymic patients and healthy subjects on recognition.
Conclusions: These results suggest that verbal retrieval deficits are stable vulnerability indicators in bipolar disorder, whereas verbal encoding deficits are manic episode indicators. The known subcortical dysfunction in this disorder may produce stable retrieval deficits while acute mood symptoms attenuate encoding during affective episodes only.     

Attention, memory, and behavioral adjustment in children with frontal lobe epilepsy

To explore whether attention, memory, and behavior would be more affected in children with frontal lobe epilepsy than in children with other types of epilepsy, we compared 16 children with frontal lobe epilepsy (FLE), 8 with temporal lobe epilepsy (TLE), and 8 with generalized absence (GEA) seizures on the Performance Speed (PS) and Freedom of Distraction (FD) indices of the WISC-III, the Continuous Performance Test (CPT), the California Verbal Learning Test (CVLT), and Rey-Osterrieth Complex Figure (ROCF). Parents completed Achenbach's Child Behavior Check List. Children with FLE scored significantly lower than the other two groups on the PS and CPT. On the CVLT they made more intrusion errors and were more prone to interference. Furthermore, they had more difficulties copying and recalling the ROCF. Behavior profiles revealed greater attention problems in this group. This may put children with FLE at greater risk of developing school problems than children with TLE and GEA.     

Effects of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on executive function in schizophrenia

BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been associated with both overall schizophrenia risk and severity of negative symptoms. This study examined whether schizophrenia patients homozygous for the risk allele (T/T) exhibit greater impairment in executive function, and determined the extent to which MTHFR's effects on negative symptoms underlie this relationship. METHODS: 200 outpatients with chronic schizophrenia were evaluated with the Verbal Fluency Test (VFT), Wisconsin Card Sort Test (WCST), and California Verbal Learning Test (CVLT). Performance was stratified by MTHFR C667T genotype. Path analysis determined the extent to which MTHFR effects on negative symptoms mediated the relationship between genotype and cognitive measures. RESULTS: T/T subjects exhibited significantly greater deficits on the VFT and had more difficulty achieving the first category on the WCST. Genotype groups did not differ in CVLT performance. C677T effects on negative symptoms contributed to, but did not fully account for, genotype effects on VFT. Negative symptoms did not mediate WCST performance. CONCLUSIONS: MTHFR C677T genotype contributes to certain executive function deficits in schizophrenia. These deficits remained significant when taking into account mediating effects of negative symptoms. Although the intermediate mechanisms for C677T effects remain uncertain, these results suggest that MTHFR-related cognitive impairment and negative symptoms reflect differing neural substrates.