Ralph A. W. Lehman

Neuropsychological and Personality Correlates of Patients’ Complaints of Disability

Clinical neuropsychologists are “concerned primarily with identifying, measuring and describing changes in behavior that relate to brain function” (Parsons, 1984). However, neuropsychologists rarely make the initial contact with a prospective patient. Rather, they are typically consulted by other professionals to help delineate the nature and meaning of a patient’s presenting symptoms and complaints. Cleeland (1976) has described this consultation process as involving a review of relevant case history material, reformulation of the referral question into a set of testable neuropsychological hypotheses, and then the examination of the patient with tests and with interview.

Diagnostic utility of the thurstone word fluency test in neuropsychological evaluations

Previous research has found that verbal associative fluency tasks are sensitive to the presence of cerebral lesions and more sensitive to frontal lobe and left hemisphere lesions than to other focal lesions. The present study investigated the diagnostic utility of the Thurstone Word Fluency Test (TWFT), a test of written verbal fluency, in detecting and localizing cerebral lesions. Using results from 203 brain-damaged and 134 normal subjects, we found that TWFT performance is affected by cerebral damage generally. At the same time, it is more impaired by frontal than by nonfrontal, by left than by right hemisphere, and by left frontal than by right frontal lesions. This test does not discriminate focal frontal from diffuse lesions. Stepwise discriminant function analyses indicated that the TWFT adds to the Halstead-Reitan Battery in discriminating focal frontal from nonfrontal lesions, but not in discriminating left hemisphere from right hemisphere lesions. Only markedly impaired TWFT performances had lateralizing significance.

Distribution and changes in strength of hand preference of cynomolgus monkeys.

Monkeys were observed for hand preference during simple reaching for food. The position of the animal relative to the food had only a slight influence upon the strength of hand preference. With repeated reaching, the strength of preference for the preferred hand tended to increase. The hand preferred on the first reach was predictive of that preferred over the entire series of 600 reaches in a significant proportion of individuals. This was not true of the animals presumed to be youngest and suggests that past experimental or developmental factors influence the hand preference displayed in later circumstances.

τ Phosphorylation in Human, Primate, and Rat Brain: Evidence that a Pool of τ Is Highly Phosphorylated In Vivo and Is Rapidly Dephosphorylated In Vitro

Abstract: The extent of τ phosphorylation is thought to regulate the binding of τ to microtubules: Highly phosphorylated τ does not bind to tubules, whereas dephosphorylated τ can bind to microtubules. It is interesting that the extent of τ phosphorylation in vivo has not been accurately determined. τ was rapidly isolated from human temporal neocortex and hippocampus, rhesus monkey temporal neocortex, and rat temporal neocortex and hippocampus under conditions that minimized dephosphorylation. In brain slices, we observed that τ isolated under such conditions largely existed in several phosphorylated states, including a pool that was highly phosphorylated; this was determined using epitope‐specific monoclonal and polyclonal antibodies. This highly phosphorylated τ was dephosphorylated during a 120‐min time course in vitro, presumably as a result of neuronal phosphatase activity. The slow‐mobility forms of τ were shifted to faster‐mobility forms following in vitro incubation with alkaline phosphatase. Laser densitometry was used to estimate the percent of τ in slow‐mobility, highly phosphorylated forms. Approximately 25% of immunoreactive τ was present as slow‐mobility (66‐ and 68‐kDa) forms of τ. The percentage of immunoreactive τ in faster‐mobility pools (42–54 kDa) increased in proportion to the decrease in content of 66–68‐kDa τ as a function of neuronal phosphatases or alkaline phosphatase treatment. These data suggest that the turnover of phosphorylated sites on τ is rapid and depends on neuronal phosphatases. Furthermore, τ is highly phosphorylated in normal‐appearing human, primate, and rodent brain. The presence of a highly phosphorylated pool of τ in adult brain may modify the present hypotheses on how paired helical filaments of Alzheimers disease are formed.

The Handedness of Rhesus Monkeys III. Consistency Within and Across Activities

The results of this study of the hand preferences of rhesus monkeys on three different tasks are threefold: (1) When retested on the same task at intervals exceeding one month virtually all individuals prefer the same hand as they did during the original test, (2) When retested on the same task, the strength of hand preference displayed by each individual is increased. (3) When tested on differing tasks, monkeys display little consistency in the laterality of hand preference or the strength of handedness expressed during different tasks. Many authors have concluded that the lack of obvious intertask consistency in the laterality of hand preference expressed by lower primates constitutes evidence for a corresponding lack of consistent laterality in the cerebral control of this behavior. This has led to them to conclude that cerebral dominance probably does not exist in these animals (Deuel, 1975; Warren, 1977). However, where data is available from the literature, including the present study, all reports show monkeys to more frequently prefer the same hand on all of the unimanual tasks they were given than would be expected by chance alone. This finding suggests that there is a weak tendency for consistent lateralization of hand usage in the monkey. Presumably, there is a corresponding predominance of the cerebral hemisphere contralateral to the preferred hand over its mate. Other studies consistent with the concept of cerebral predominance in the monkey were reviewed. These findings do not constitute evidence for cerebral dominance in the monkey akin to that found in man. They do suggest that when performing certain activities, monkeys may have one hemisphere predominant over the other even though the degree and laterality of predominance may vary greatly from one individual and task to another.

Sensitivity of figural fluency on the five-point test to focal neurological dysfunction

Abstract The Five-Point test, a measure of nonverbal figural fluency created by Regard, Strauss, and Knapp (1982), was administered to 258 patients (196 with neurologic disease and 62 with psychiatric disorders) to provide information on the sensitivity of the measure to frontal lobe dysfunction. Patients with frontal lobe dysfunction had a significantly higher percentage of perseverative errors than did nonfrontal neurologic and psychiatric patients on two versions of the Five-Point test. Furthermore, patients with right frontal lobe dysfunction were more often correctly classified as defective on the basis of percent perseveration than patients with cerebral dysfunction in other brain regions. These data provide evidence of the sensitivity of the Five-Point test to brain damage generally and to frontal lobe dysfunction specifically.

In vitro hypoxia and excitotoxicity in human brain induce calcineurin-Bcl-2 interactions.

Although pathogenesis of neuronal ischemia is incompletely understood, evidence indicates apoptotic neuronal death after ischemia. Bcl-2, an anti-apoptotic and neuroprotective protein, interacts with calcineurin in non-neuronal tissues. Activation of calcineurin, which is abundant in the brain, may play a role in apoptosis. Using co-immunoprecipitation experiments in biopsy-derived, fresh human cortical and hippocampal slices, we examined possible interactions between calcineurin and Bcl-2. Calcineuin-Bcl-2 interactions increased after exposure in vitro to excitotoxic agents and conditions of hypoxia/aglycia. This interaction may shuttle calcineurin to substrates such as the inositol-1,4,5-tris-phosphate receptor because under these experimental conditions interactions between calcineurin and inositol-1,4,5-tris-phosphate receptor also increased. A specific calcineurin inhibitor, FK-520, attenuated insult-induced increases in calcineurin-Bcl-2 interactions and augmented caspase-3 like activity. These data suggest that Bcl-2 modulates neuroprotective effects of calcineurin and that calcineurin inhibitors increase ischemic neuronal damage.

Cerebral glucose utilization after aversive conditioning and during conditioned fear in the rat

Regional cerebral glucose utilization (rCMRglu) was studied in rats with and without previous aversive conditioning. Four groups of rats were studied. Two groups of rats were aversely conditioned by placing them in a shock chamber (conditioned stimulus) where they received random footshocks. The two remaining groups were placed in the shock chamber but not conditioned. Regional CMRglu and systemic parameters (heart rate, mean arterial blood pressure (MABP), blood gases and pH, plasma catecholamines, and plasma glucose) were measured in unconditioned and conditioned rats in the presence and in the absence of the conditioned stimulus. The changes in rCMRglu described below appeared to be global and not limited to specific regions. Results are as follows: (1) transferring unconditioned rats to the shock chamber had no significant effect on rCMRglu even though the systemic parameters indicated a stress response. It appears that stress capable of inducing changes in heart rate, MABP, and plasma catecholamines is not necessarily accompanied by increases in cerebral glucose utilization. (2) Conditioned rats not exposed to the shock chamber at the time rCMRglu was measured had decreased rates of rCMRglu compared to rats that were not conditioned. Except for plasma epinephrine, which increased after conditioning, systemic parameters were not affected. (3) Conditioned fear, elicited by transferring conditioned rats to the shock chamber, increased rCMRglu when compared to a control group that was conditioned to footshock using the same paradigm but not exposed to the shock chamber at the time rCMRglu was measured. The systemic parameters indicated a stress response in conditioned rats transferred to the shock chamber.(ABSTRACT TRUNCATED AT 250 WORDS)

Microtubule assembly competence analysis of freshly-biopsied human tau, dephosphorylated tau, and Alzheimer tau.

Phosphorylation of the microtubule‐associated protein tau regulates its binding to microtubules; highly phosphorylated tau is also a prime component of paired helical filaments (PHFs) of Alzheimers disease (AD). Tau from freshly biopsied human, monkey, and rat brain share similar electrophoretic mobility patterns and overlapping phosphorylated epitopes when compared to AD tau isolated from AD brain. We compared the microtubule reassembly competence of fresh isolates of phosphorylated tau to that of maximally dephosphorylated tau and tau from AD brain. A rapid procedure was developed which permitted the enrichment of phosphorylated and dephosphorylated tau from human biopsies in the absence of protein kinase and phosphatase activity. Microtubule assembly assays, using a spectrophotometric measure and purified bovine brain tubulin, were used to correlate assembly competence with states of tau electrophoretic mobility. Maximally dephosphorylated human biopsy‐derived tau and monkey tau were assembly competent; tau from AD brain was virtually unable to direct microtubule assembly. Unmodified, biopsy‐derived tau from non‐AD brain was intermediate in assembly competence relative to AD tau and dephosphorylated tau. Several lines of evidence were used to correlate phosphorylation states of tau with microtubule assembly. First, in vitro dephosphorylation of human biopsy‐derived tau with either PP2A or PP2B alone or in combination led to increasing assembly competence as the electrophoretic mobility of tau increased. Second, addition of the protein phosphatase inhibitor okadaic acid (10 μM) to brain‐slice preparations slowed electrophoretic mobility of tau and decreased binding competence. We suggest that tau derived from freshly‐biopsied brain exists in a range of phosphorylated states, and that dephosphorylation by PP2A and/or PP2B increases microtubules assembly competence.

Hand preferences of rhesus monkeys on differing tasks

In a replication study, monkeys were tested for hand preference on three differing tasks: simple reaching for food presented on a board, choice of hand during a visual discrimination task and retrieval of food pellets from a row. Both laterality and degree of hand preference correlated significantly on two of the three tasks. Extremely little correlation was found across the other task combinations. Consistency of hand preference was greater within repetitions of a task than between any two tasks. The implication of these findings upon the search for a cerebral dominance underlying hand preference in the monkey is discussed.