Circling behavior following systemic d-amphetamine administration: Potential noradrenergic and dopaminergic involvement

Systemic treatment with d-amphetamine produced a dose-dependent increase in the circling behavior of normal mice. Treatment with both -methyl-p-tyrosine (-MpT) and FLA-63 antagonized the amphetamine-induced circling behavior. Similarly, blockade of B-adrenergic receptors by propranolol and dopamine receptors by haloperidol reversed the circling response elicited by amphetamine. In contrast to -MpT and haloperidol, however, neither FLA-63 nor propranolol attenuated the locomotor excitation engendered by amphetamine. Following repeated d-amphetamine injections the circling ordinarily induced by a single injection was abolished, whereas the locomotor effects of amphetamine remained unaltered. These findings are consistent with earlier work suggesting that tolerance may occur in those behaviors that involve a noradrenergic component.     

Systematic information processing style and perseverative worry

This review examines the theoretical rationale for conceiving of systematic information processing as a proximal mechanism for perseverative worry. Systematic processing is characterised by detailed, analytical thought about issue-relevant information, and in this way, is similar to the persistent, detailed processing of information that typifies perseverative worry. We review the key features and determinants of systematic processing, and examine the application of systematic processing to perseverative worry. We argue that systematic processing is a mechanism involved in perseverative worry because (1) systematic processing is more likely to be deployed when individuals feel that they have not reached a satisfactory level of confidence in their judgement and this is similar to the worrier's striving to feel adequately prepared, to have considered every possible negative outcome/detect all potential danger, and to be sure that they will successfully cope with perceived future problems; (2) systematic processing and worry are influenced by similar psychological cognitive states and appraisals; and (3) the functional neuroanatomy underlying systematic processing is located in the same brain regions that are activated during worrying. This proposed mechanism is derived from core psychological processes and offers a number of clinical implications, including the identification of psychological states and appraisals that may benefit from therapeutic interventions for worry-based problems.     

Effects of phonological and semantic deficits on facilitative and inhibitory consequences of item repetition in spoken word comprehension

Repeating a word can have both facilitative and inhibitory effects on subsequent processing. The present study investigated these dynamics by examining the facilitative and inhibitory consequences of different kinds of item repetition in two individuals with aphasia and a group of neurologically intact control participants. The two individuals with aphasia were matched on overall aphasia severity, but had deficits at different levels of processing: one with a phonological deficit and spared semantic processing, the other with a semantic deficit and spared phonological processing. Participants completed a spoken word-to-picture matching task in which they had to pick which of four object images matched the spoken word. The trials were grouped into pairs such that exactly two objects from the first trial in a pair were present on screen during the second trial in the pair. When the second trial's target was the same as the first trial's target, compared to control participants, both participants with aphasia exhibited equally larger repetition priming effects. When the second trial's target was one of the new items, the participant with a phonological deficit exhibited a significantly more negative effect (i.e., second trial response slower than first trial response) than the control participants and the participant with a semantic deficit. Simulations of a computational model confirmed that this pattern of results could arise from (1) normal residual activation being functionally more significant when overall lexical processing is slower and (2) residual phonological activation of the previous trial's target having a particularly strong inhibitory effect specifically when phonological processing is impaired because the task was phonologically-driven (the spoken input specified the target). These results provide new insights into perseveration errors and lexical access deficits in aphasia.     

Effects of rat ventral and dorsal hippocampus temporal inactivation on delayed alternation task

To determine the involvement of the hippocampal regions in a operant-type delayed alternation task of short delay or long delay, microinjections of muscimol into the hippocampus were used for temporal inactivation during the behavioral test in each rat. Dorsal hippocampal inactivation impaired the correct ratio of long delay. Ventral hippocampal inactivation showed no changes in the correct ratio, however, it increased the tendency of perseveration in long delay. These findings suggest hippocampus has regional differentiation in delayed alternation task.     

Adults with Autism Show Increased Sensitivity to Outcomes at Low Error Rates During Decision-Making

Decision-making is an important function that can be quantified using a two-choice prediction task. Individuals with Autistic Disorder (AD) often show highly restricted and repetitive behavior that may interfere with adaptive decision-making. We assessed whether AD adults showed repetitive behavior on the choice task that was unaffected by changing task demands, by examining the influence of experimenter-determined error rates on decision-making. Sixteen AD adults and 14 typically developed subjects were administered a two-choice task using three error rate conditions. Although AD subjects showed occurrences of stereotyped responding, their decision-making behavior was strongly affected by changes in task demands, especially when they experienced frequent success. Thus, behavioral paradigms that provide frequent reinforcement may be helpful in modifying decision-making abilities in AD.     

Effects of medial septal lesions on operant delayed alternation in rats

The septohippocampal system regulates spatial behavior, memory and response flexibility. This experiment determined which of these functions is disrupted by medial septal lesions which impair operant delayed alternation in rats. Male hooded rats received either medial septal lesions or a control operation. Following recovery, they were reinforced for alternating left and right lever presses in an operant chamber. The effects of various delays (0, 10 and 20 s), and exteroceptive cues were assessed. Medial septal lesions did not impair alternation performance at the 0-s delay, but did produce severe impairments at the 10- and 20-s delays. An exteroceptive light cue which reduced the spatial requirements of the task did not ameliorate this impairment. However, an exteroceptive light cue which reduced the working-memory requirements of the task did ameliorate the lesion-induced deficit on delayed alternation. While the lesioned rats also made more perseverative errors than the controls, statistically removing this influence from the data did not modify the results. These data suggest that medial septal lesions in rats impair operant delayed alternation by disrupting the general process of working-memory rather than spatial behavior or response flexibility.     

Attenuation of perseverative behavior after repeated amphetamine treatment: Tolerance or attentional deficits?

When permitted to explore an 8-arm radial maze, animals exhibited a systematic pattern of exploration characterized by preference for the most novel arms (spontaneous alternation) and entry into immediately adjacent arms (adjacent alternation). Acute treatment with moderate dosages of amphetamine reduced the proportion of both types of alternation responses and induced marked stimulus perseveration, i.e., consecutive entries between pairs of arms. Prior exposure to the apparatus enhanced the degree of perseveration ordinarily observed, and provoked perseveration after low doses of the drug. In contrast to acute drug treatment, perseveration was reduced after chronic amphetamine administration. However, chronic amphetamine treatment did not appear simply to reduce the potency of the drug. In contrast to the effects of apparatus pre-exposure on the degree of perseveration induced by acute amphetamine treatment, the degree of perseveration was not enhanced by pre-exposure to the maze in mice with a history of chronic amphetamine administration. Moreover, the exploratory pattern evident in chronically treated animals differed from that of control animals even when tested in the nondrug state. That is, animals chronically treated with amphetamine and tested with saline exhibited alternation scores which did not deviate from chance. These data suggest that chronic amphetamine treatment alters the way in which organisms attend, or respond, to environmental stimuli.     

Behavioral consequences of perinatal hypothyroidism in postnatal and adult rats

The long-term effects of perinatal hypothyroidism on spontaneous locomotor behaviors were assessed after exposure to the antithyroid drug, methimazole. Perseveration was observed in methimazole-treated rats in a spatial maze. Locomotor activity in residential mazes was examined at 6 weeks, 4 months, and 6 months of age. Treated rats were hypoactive at some intervals compared with controls and were hyperactive at others. These paradoxical differences resulted from changes in exploratory, diurnal, and nocturnal locomotor activity in control rats both with increasing age and on repeated exposures to residential mazes; rats after perinatal hypothyroidism had relatively constant levels of activity on repeated days of exposure to residential mazes and at different ages. These results may be related to perseveration noted in the spatial maze. In an analysis of walking patterns, treated rats tended to have a more pronounced asymmetry in gait than controls.     

A pattern of perseveration in cocaine addiction may reveal neurocognitive processes implicit in the Wisconsin Card Sorting Test

The ability to adapt behavior in a changing environment is necessary for humans to achieve their goals and can be measured in the lab with tests of rule-based switching. Disease models, such as cocaine addiction, have revealed that alterations in dopamine interfere with adaptive set switching, culminating in perseveration. We explore perseverative behavior in individuals with cocaine use disorders (CUD) and healthy controls (CON) during performance of the Wisconsin Card Sorting Test (WCST) (N = 107 in each group). By examining perseverative errors within each of the 6 blocks of the WCST, we uniquely test two forms of set switching that are differentiated by either the presence (extradimensional set shifting (EDS) - first 3 blocks) or absence (task-set switching - last 3 blocks) of new contingency learning. We also explore relationships between perseveration and select cognitive and drug use factors including verbal learning and memory, trait inhibitory control, motivational state, and urine status for cocaine (in CUD). Results indicate greater impairment for CUD than CON on the WCST, even in higher performing CUD who completed all 6 blocks of the WCST. Block by block analysis conducted on completers’ scores indicate a tendency for greater perseveration in CUD than CON but only during the first task-set switch; no such deficits were observed during EDS. This task-set switching impairment was modestly associated with two indices of immediate recall (r = −.32, −.29) and urine status for cocaine [t (134) = 2.3, p < .03]. By distinguishing these two forms of switching on the WCST, the current study reveals a neurocognitive context (i.e. initial stage of task-set switching) implicit in the WCST that possibly relies upon intact dopaminergic function, but that is impaired in CUD, as associated with worse recall and possibly withdrawal from cocaine. Future studies should investigate whether dopaminergically innervated pathways alone, or in combination with other monoamines, underlie this implicit neurocognitive processes in the WCST.     

Monocular patching affects inattention but not perseveration in spatial neglect

Monocular patching might improve perceptual-attentional, not motor-intentional deficits in a patient with chronic post-stroke left spatial neglect. Performing a line-cancellation task, his omission errors were associated with a perceptual-attentional ‘where’ deficit, while perseverative errors were associated with ‘aiming’ motor-intentional bias. Contralesional patching had no effect on the omissions (p?=?.871), whereas ipsilesional patching reduced left-sided omissions compared with the unpatched condition (p?=?.016). Neither patching condition altered perseverative errors. Further research is needed to examine whether targeting treatments to spatial neglect symptoms (omissions, perseveration) results in improved outcomes.