Neuropsychological Measures which Discriminate Among Adults with Residual Symptoms of Attention Deficit Disorder and Other Attentional Complaints

Attention Deficit Disorder (ADD) in children is accompanied by quantifiable deficits on attentional, learning, and memory indices. Symptoms of childhood ADD persist into adulthood in many cases. However, many adults without a history of childhood ADD also complain of difficulties with attention, presumably due to other etiologies than developmental ADD. This study investigated whether performance on neuropsychological measures of attention and memory could differentiate adults with attentional complaints and history of childhood ADD from those without childhood ADD. Adults with a history of childhood ADD demonstrated reduced scores on the Paced Auditory Serial Addition Task and Delayed Free Recall on the California Verbal Learning Test as well as on a verbal fluency task relative to adults who denied attentional problems in childhood. Discriminant function analysis using verbal fluency, performance on the Wisconsin Card Sorting Test, verbal learning and recall, Digit Span Backward, and performance on the Paced Auditory Serial Addition Task as predictors correctly classified adults with and without a history of childhood ADD into diagnostic groups with 75% accuracy.     

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.     

Deficit in decision making in catatonic schizophrenia: an exploratory study

Catatonic schizophrenia can be distinguished from paranoid schizophrenia by prominent behavioral and motor anomalies. As demonstrated in recent imaging studies, behavioral symptoms may be related to dysfunction in the ventral prefrontal cortex. However, the neuropsychological correlates of ventral prefrontal cortical dysfunction remain unclear. In an exploratory study, we investigated eight patients with catatonic schizophrenia and compared them with 19 patients with paranoid schizophrenia and 26 healthy subjects. The Iowa Gambling Task (IGT) and the Object Alternation Task (OAT) served as measures of ventral prefrontal cortical function. In addition, other prefrontal cortical tests such as a visual working memory task, a Go-NoGo task, and the Wisconsin Card Sorting Test, as well as attentional tasks, were included in the test battery. Catatonic patients showed significant deficits in the IGT characterized by an inability to shift from the initial preference for high-risk cards to a more advantageous strategy with low-risk cards. Moreover, catatonic patients showed significant deficits in the OAT. In conclusion, our preliminary results suggest a specific deficit in catatonic schizophrenia in those neuropsychological measures that are associated with ventral prefrontal cortical function.     

Verbal memory retrieval deficits associated with untreated hypothyroidism

The effects of inadequate thyroid hormone availability to the brain on adult cognitive function are poorly understood. This study assessed the effects of hypothyroidism on cognitive function using a standard neuropsychological battery in 14 patients suffering from untreated hypothyroidism and complaining of subjective cognitive difficulties in comparison with 10 age-matched healthy comparison subjects. Significant differences between groups were limited to verbal memory retrieval as measured by the California Verbal Learning Test (CVLT). On short delay free recall, long delay free recall, and long delay cued recall, significant differences remained between groups despite the limited statistical power of this study. There were no significant results found between groups on attentional or nonverbal tasks. Results suggest that hypothyroid-related memory deficits are not attributable to an attentional deficit but rather to specific retrieval deficits.     

Role of the amygdala in decisions under ambiguity and decisions under risk: evidence from patients with Urbach-Wiethe disease

Various neuropsychological studies have shown that decision-making deficits can occur in a wide range of patients with brain damage or dysfunctions. Decisions under ambiguity, as measured with the Iowa Gambling Task, primarily depend on the integrity of the ventromedial prefrontal cortex and the amygdala, as well as on further brain regions such as the somatosensory cortex. However, little is known about the specific role of these structures in decisions under risk measured with tasks that offer explicit rules for gains and losses and winning probabilities, for example, the Game of Dice Task. We aimed to investigate the potential role of the amygdala for decisions under risk. For this purpose, we examined three patients with Urbach-Wiethe disease--a rare syndrome associated with selective bilateral mineralisation of the amygdalae. Neuropsychological performance was assessed with the Iowa Gambling Task (decisions under ambiguity), the Game of Dice Task (decisions under risk), and an extensive neuropsychological test battery focussing on executive functions. Furthermore, previous studies found relationships between generating skin conductance responses and deciding advantageously in the Iowa Gambling Task. Accordingly, we recorded skin conductance responses during both decision tasks as a measure of emotional reactivity. Results indicate that patients with selective amygdala damage have lower scores in both decisions under ambiguity and decisions under risk. Decisions under risk are especially compromised in patients who also demonstrate deficits in executive functioning. In both gambling tasks, patients showed reduced skin conductance responses compared to healthy comparison subjects. The results suggest that deciding advantageously under risk conditions involves both the use of feedback from previous trials, as required by decisions under ambiguity, and in addition, executive functions.     

Characteristics of memory dysfunction in body dysmorphic disorder.

Although body dysmorphic disorder (BDD) is receiving increasing empirical attention, very little is known about neuropsychological deficits in this disorder. The current study investigated the nature of memory dysfunction in BDD, including the relationship between encoding strategies and verbal and nonverbal memory performance. We evaluated 17 patients with BDD and 17 healthy controls using the Rey-Osterrieth Complex Figure Test (RCFT) and the California Verbal Learning Test (CVLT). BDD patients differed significantly from healthy controls on verbal and nonverbal learning and memory indices. Multiple regression analyses revealed that group differences in free recall were statistically mediated by deficits in organizational strategies in the BDD cohort. These findings are similar to patterns previously observed in obsessive-compulsive disorder (OCD), suggesting a potential relationship between OCD and BDD. Studies in both groups have shown that verbal and nonverbal memory deficits are affected by impaired strategic processing.     

Basal-corticofrontal circuits in schizophrenia and obsessive-compulsive disorder: a controlled, double dissociation study.

BACKGROUND: Several lines of research suggest that prefrontal cortex dysfunctions observed in obsessive compulsive disorder (OCD) and schizophrenia (SKZ) are linked to two partially independent neuroanatomic systems: the ventromedial prefrontal cortex and the dorsolateral prefrontal cortex, with different neuroanatomic connections, including the striatum. The primary aim of this study was to test this hypothesis using a double dissociation study of neuropsychological tasks performance of the dorsolateral prefrontal cortex and ventromedial prefrontal cortex. METHODS: We administered the Wisconsin Card Sorting Test, the Gambling Task, and the four-disk version of the Tower of Hanoi to 110 SKZ and 67 OCD patients and 56 control subjects. RESULTS: A clear double dissociation of Wisconsin Card Sorting Test and Gambling Task performances was found, with SKZ patients performing the Wisconsin Card Sorting test significantly worse than OCD patients and control subjects and OCD patients performing the Gambling Task significantly worse than SKZ and control subjects. Both SKZ and OCD patients performed the Tower of Hanoi significantly worse than control subjects. CONCLUSIONS: Results from our double dissociation study confirm the hypothesis of involvement of different frontal lobe subsystems within basal-corticofrontal circuits function in SKZ and OCD.     

The contributions of lesion laterality and lesion volume to decision-making impairment following frontal lobe damage

Lesions to prefrontal cortex (PFC) in humans can severely disrupt everyday decision-making, with concomitant effects on social and occupational functioning. Forty-six patients with unilateral lesions to prefrontal cortex and 21 healthy control subjects were administered three neuropsychological measures of decision-making: the Iowa Gambling Task, the Cambridge Gamble Task, and the Risk Task. Magnetic resonance imaging (MRI) scans were acquired from 40 patients, with region of interest (ROI) mapping of prefrontal subregions. The frontal patients showed only limited damage in medial and orbital prefrontal cortex, but greater damage in lateral prefrontal regions of interest. Patients with right frontal lesions preferred the risky decks on the Iowa Gambling Task, and differed significantly from left frontal and control subjects. Within the right frontal group, the preference for the risky decks was correlated with the total lesion volume and the volume of damage outside of the ventromedial prefrontal region. Right and left frontal groups did not differ significantly on the Cambridge Gamble Task or the Risk Task, and performance was not associated with lesion volume. The results indicate a laterality effect on the Iowa Gambling Task, and the contribution of prefrontal regions outside the ventromedial region to task performance. The Cambridge Gamble Task and Risk Task were less sensitive to the effects of unilateral frontal lobe lesions, and may be more selectively associated with ventral prefrontal damage.     

Dissociation of decisions in ambiguous and risky situations in obsessive–compulsive disorder

Patients with obsessive–compulsive disorder (OCD) often show deficits in everyday decision-making, a phenomenon which is leading to a growing research interest in neuropsychological aspects of decision-making in OCD. Previous investigations of OCD patients demonstrated deficits in the Iowa Gambling Task (IGT), a decision-making task with implicit rules. Results were interpreted as reflecting orbitofrontal cortex dysfunctions observed in OCD. The aim of the present study is to investigate OCD patients' performance on the Game of Dice Task (GDT), a decision-making task with explicit and stable rules. For this purpose, 23 patients with OCD and 22 healthy comparison subjects were examined with the GDT and the IGT as well as with tests of executive functioning. While patients performed worse than comparison subjects on the IGT, they were unimpaired on the GDT and executive functioning tasks. Results further emphasize dysfunctions of the orbitofrontal cortex, but indicate intact functioning of the dorsolateral prefrontal cortex in patients with OCD.     

Functional MRI of sustained attention in bipolar mania

We examined sustained attention deficits in bipolar disorder and associated changes in brain activation assessed by functional magnetic resonance imaging (fMRI). We hypothesized that relative to healthy participants, those with mania or mixed mania would (1) exhibit incremental decrements in sustained attention over time, (2) overactivate brain regions required for emotional processing and (3) progressively underactivate attentional regions of prefrontal cortex. Fifty participants with manic/mixed bipolar disorder (BP group) and 34 healthy comparison subjects (HC group) received an fMRI scan while performing a 15-min continuous performance task (CPT). The data were divided into three consecutive 5-min vigilance periods to analyze sustained attention. Composite brain activation maps indicated that both groups activated dorsal and ventral regions of an anterior-limbic network, but the BP group exhibited less activation over time relative to baseline. Consistent with hypotheses 1 and 2, the BP group showed a marginally greater behavioral CPT sustained attention decrement and more bilateral amygdala activation than the HC group, respectively. Instead of differential activation in prefrontal cortex over time, as predicted in hypothesis 3, the BP group progressively decreased activation in subcortical regions of striatum and thalamus relative to the HC group. These results suggest that regional activation decrements in dorsolateral prefrontal cortex accompany sustained attention decrements in both bipolar and healthy individuals. Stable amygdala overactivation across prolonged vigils may interfere with sustained attention and exacerbate attentional deficits in bipolar disorder. Differential striatal and thalamic deactivation in bipolar disorder is interpreted as a loss of amygdala (emotional brain) modulation by the ventrolateral prefrontal-subcortical circuit, which interferes with attentional maintenance.     

Neuropsychological disturbances and cerebral blood flow in bipolar disorder

OBJECTIVE: To determine and correlate alterations in neuropsychological function and cerebral blood flow in bipolar patients. METHOD: Assessments included the Positive and Negative Symptom Scale, Global Assessment Functioning, Wechsler Adult Intelligence Scale (WAIS), Wisconsin Card Sorting Test (WCST), Stroop test, Trail Making Test (TMT), California Verbal Learning Test (CVLT), Wechsler Memory Scale (WMS) and phonetic verbal fluency/controlled oral word association tests. Single photon emission computed tomography (SPECT) was carried out with the administration of 99mTc-HMPAO. Forty-three outpatients out of 85 fulfilling RDC diagnostic criteria for bipolar disorder and six healthy subjects were included in the study. SPECT and neuropsychological assessments were performed in 30 patients in manic (n = 7), hypomanic (n = 8), depressed (n = 12) or euthymic (n = 3) states. All assessments were carried out before starting treatment. RESULT: Several corrected correlations between neuropsychological function and cerebral blood flow (CBF) were identified: executive function (WCST) and striatal, frontal, temporal, cerebellum, parietal and cingulate CBF; memory (WMS, WAIS-Digits) and striatal, frontal, temporal and parietal CBF; attentional tasks (Stroop) and striatal, temporo-medial and parietal CBF; verbal learning (CVLT) and frontal, posterior temporal, cingulate and occipital CBF; psychomotor disturbances (TMT) and anterior temporal CBF; poorer intelligence performance scores (WAIS-Vocabulary) and cerebellum and parietal CBF. CONCLUSIONS: This study confirms the presence of functional disturbances in fronto-subcortical structures, the cerebellum and limbic system in bipolar patients.     

Cognitive correlates of under-ambiguity and under-risk decision making in high-functioning patients with relapsing remitting multiple sclerosis

Introduction: Impairment of decision making in relapsing remitting multiple sclerosis is still controversial, and its neuropsychological correlates have never been explored thoroughly, especially in patients with minimal physical and cognitive deficits. In the present study we investigated the cognitive underpinnings of decision making under ambiguous and explicit conditions in patients with very mild relapsing remitting multiple sclerosis, using a dice and a card gambling game. Method: The study sample included 60 patients and 35 healthy subjects. In the Game of Dice Task, winning and losing probabilities are obvious to the subject, while in the Iowa Gambling Task they are initially ambiguous and have to be gradually identified. Performance at the two tasks was correlated with scores obtained at tests investigating cognitive processing speed, memory, language and executive functions. Results: Patients’ performance did not differ from that of controls at either gambling task. There was only a trend for them to be significantly slower than healthy subjects in progressively recognizing advantageous decks in the Iowa Gambling Task. While the Game of Dice was unrelated to neuropsychological tests, predictors of performance at the Iowa task were Letter Fluency and the Symbol Digit Modalities Test for the initial, under-ambiguity, trials and the Wisconsin Card Sorting Test for the last, purely under-risk, trials. Conclusions: Our results suggest that high-functioning patients with relapsing remitting multiple sclerosis are substantially capable of making advantageous decisions, even if they may be slower in processing options and shifting strategy when selection criteria are not explicit.     

Neuropsychological performance in pediatric bipolar disorder.

BACKGROUND: Growing awareness of childhood bipolar disorder necessitates further cognitive neuroscience research to determine unique developmental differences between pediatric and adult onset bipolar disorder. We sought to examine whether neuropsychological function in children with bipolar disorder resembles that in adults with the illness and to extend our knowledge about cognitive function in pediatric bipolar disorder. METHODS: We administered a computerized neuropsychological test battery known as the Cambridge Neuropsychological Test Automated Battery to a sample of 21 children and adolescents with bipolar disorder and compared them with 21 age- and gender-matched controls. RESULTS: In comparison to controls, children with bipolar disorder were impaired on measures of attentional set-shifting and visuospatial memory. Post hoc analyses in pediatric bipolar disorder subjects did not show significant associations between neuropsychological performance and manic symptomatology or attention-deficit/hyperactivity disorder comorbidity. CONCLUSIONS: Cambridge Neuropsychological Test Automated Battery data presented here in pediatric bipolar disorder fit well within the broader framework of known neurocognitive deficits in adult bipolar disorder. Our pediatric bipolar disorder subjects demonstrated selective deficiencies in attentional set-shifting and visuospatial memory. Our work suggests altered ventrolateral prefrontal cortex function, especially when linked to other lesion and neuroimaging studies.     

Neuropsychological and oculomotor correlates of spatial working memory performance in schizophrenia patients and controls.

Recent reports of spatial working memory deficits in schizophrenia provide evidence for dorsolateral prefrontal cortical (DLPFC) dysfunction. However, the question of how spatial working memory performance relates to other task impairments in schizophrenia considered reflective of frontal dysfunction, such as the Wisconsin Card Sorting Test (WCST) and smooth pursuit eye tracking, has been largely unexplored. Spatial working memory, as measured by a computerized visual-manual delayed response task (DRT), was evaluated in 42 schizophrenia patients and 54 normal controls. Subjects also completed a battery of neuropsychological and oculomotor tasks. Schizophrenia patients performed as accurately as controls on a no-delay, sensory-motor control condition, but showed a significant impairment in spatial accuracy with the addition of an 8-s delay and verbal distraction task. For the patients, working memory impairment was associated with fewer categories on the WCST, impaired eye tracking, fewer words learned on the Rey Auditory Verbal Learning Test, but not with measures of general cognitive and clinical functioning. Results suggest the presence of a sub-group of schizophrenia patients with common pathophysiology that accounts for the co-variance of several tasks implicating prefrontal dysfunction.     

The effect of previous psychotic mood episodes on cognitive impairment in euthymic bipolar patients

OBJECTIVES: Cognitive dysfunctions in several domains were proposed to be trait markers of bipolar patients. The aim of this study was to evaluate the effect of previous psychotic features on neuropsychological measures, including sustained attention, in remitted bipolar patients. METHODS: The study participants were 40 euthymic psychotic, 25 non-psychotic bipolar I patients and 30 healthy control subjects. Participants were assessed with a battery of neuropsychological tests targeting attention, executive functions, psychomotor speed, verbal learning and memory. RESULTS: Euthymic psychotic bipolar patients performed worse than controls on most of the measures, after controlling for the confounding effects of education, age and residual symptoms. Non-psychotic patients were also impaired on tasks of attention, fluency and psychomotor speed. 'Number of Wisconsin Card Sorting Test (WCST) categories' achieved was the only measure on which psychotic patients performed significantly worse compared to non-psychotic patients. Differences among patient groups were not explained by illness severity measures. The duration of illness was related to slowness in psychomotor speed tasks. Verbal memory deficits may be related to serum lithium levels and age of onset of disease. CONCLUSIONS: Deficits in cognitive flexibility may be a candidate for being a trait marker of psychotic features among bipolar patients. However, verbal fluency, psychomotor speed and sustained attention deficits may be candidates for vulnerability indicators of bipolar disorder in general.     

Impairment of verbal memory and learning in antipsychotic-naïve patients with first-episode schizophrenia

BACKGROUND: Verbal memory deficits are of interest in schizophrenia because of the potential relationship to functional and anatomic mesial temporal lobe pathology in this disorder. The goal of this study was to characterize the nature of verbal memory impairments in antipsychotic-na?ve schizophrenic patients early in the course of illness. METHODS: Neuroleptic-na?ve patients with schizophrenia (n=62) and healthy individuals (n=67), matched on IQ, age, sex, and parental socioeconomic status, were administered the California Verbal Learning Test (CVLT). RESULTS: Schizophrenia participants performed significantly worse than healthy individuals on measures of verbal learning, short- and long-term memory, and immediate attention. Deficits in recall were related to reduced use of organizational strategies to facilitate verbal encoding and retrieval. No group differences were found in rate of forgetting or susceptibility to proactive or retroactive interference. Memory deficits had minimal relation to positive or negative symptom severity. CONCLUSIONS: Schizophrenia is characterized by significant verbal memory dysfunction early in the course of illness prior to treatment with antipsychotic medications. Deficits in consistency of learning over several trials, as well as a strong relationship between semantic organizational strategies and reduced learning capacity, implicate prefrontal dysfunction as a contributor to verbal memory deficits in schizophrenia.     

Effect of the dopamine D2 receptor T allele on response latency after mild traumatic brain injury

OBJECTIVE: The authors tested the hypothesis that the dopamine D2 receptor T allele (formerly described as the A1 allele) would be associated with poorer performance on memory and attention tasks following mild traumatic brain injury. METHOD: Thirty-nine patients with mild traumatic brain injury and 27 comparison subjects were genotyped. All subjects completed memory and attention tests, including the California Verbal Learning Test recognition task and the Continuous Performance Test. RESULTS: In both groups the T allele was associated with poorer performance on the California Verbal Learning Test recognition task. There was also a significant diagnosis-by-allele interaction on measures of response latency (Continuous Performance Test): the subjects with mild traumatic brain injury and the T allele had the worst performance. CONCLUSIONS: Genetic polymorphisms modulating central dopaminergic tone can affect cognitive outcome following mild traumatic brain injury.     

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.     

Delayed transition from ambiguous to risky decision making in alcohol dependence during Iowa Gambling Task

It has been demonstrated that alcohol-dependent patients exhibit decision-making deficits, particularly, hypersensitivity to reward and executive dysfunction. Yet, how the impaired motivational process and executive dysfunction in the patients affect decisions under ambiguity and risk with different degrees of uncertainty is little known. To investigate the neuropsychological origin of the impaired decision making under uncertainty in alcohol dependence, we administered the Iowa Gambling Task (IGT), Game of Dice Task (GDT) and Wisconsin Card Sorting Test (WCST) to 23 alcohol-dependent patients and 21 healthy subjects, and calculated the correlations between the task performances. We found that the patients showed poor performance in all three tasks compared with the healthy subjects. Moreover, correlations between performances on the GDT and the later trials of the IGT were delayed in alcohol-dependent patients when compared with healthy subjects. There is also a significant correlation between performances of earlier trials of the IGT and the WCST in the patients. These findings suggest that executive dysfunction in alcohol-dependent patients hampers appropriate estimation of probability distributions of possible alternatives, leading to a delayed transition from ambiguous to risky conditions in the Iowa Gambling Task.