Working and long-term memory deficits in schizophrenia: Is there a common prefrontal mechanism?

This study tested the hypothesis that dorsolateral prefrontal cortex deficits contribute to both working memory and long-term memory disturbances in schizophrenia. It also examined whether such deficits were more severe for verbal than nonverbal stimuli. Functional magnetic resonance imaging was used to assess cortical activation during performance of verbal and nonverbal versions of a working memory task and both encoding and recognition tasks in 38 individuals with schizophrenia and 48 healthy controls. Performance of both working memory and long-term memory tasks revealed disturbed dorolateral prefrontal cortex activation in schizophrenia, although medial temporal deficits were also present. Some evidence was found for more severe cognitive and functional deficits with verbal than nonverbal stimuli, although these results were mixed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal and spatial context memory in patients with focal frontal, temporal lobe, and diencephalic lesions

Patients with focal frontal, temporal lobe, or diencephalic lesions were investigated on measures of temporal (recency) and spatial (position) context memory, after manipulating exposure times to match recognition memory for targets (pictorial stimuli) as closely as possible. Patients with diencephalic lesions from an alcoholic Korsakoff syndrome showed significant impairment on the temporal context (recency) task, as did patients with frontal lesions penetrating the dorsolateral frontal cortex, according to MRI (and PET) evidence. Patients with temporal lobe lesions showed only a moderate (non-significant) impairment on this task, and patients with medial frontal lesions, or large frontal lesions not penetrating the dorsolateral cortical margins, performed as well as healthy controls at this task. On the spatial context memory task, patients with lesions in the temporal lobes showed significant impairment, and patients with right temporal lesions performed significantly worse than patients with left temporal lesions. Patients with diencephalic lesions showed only a modest (non-significant) impairment on this task, and the frontal lobe group performed normally. When a group of patients with temporal lobe lesions resulting from herpes encephalitis were examined separately, an identical pattern of results was obtained, the herpes group being significantly impaired on spatial memory and showing a trend towards impairment for temporal context memory. There were strong correlations between anterograde memory quotients and context memory performance (despite the use of an exposure time titration procedure) and a weak association in the frontal group with one frontal/executive task [corrected] (card-sorting perservations). It is predicted that correlations between temporal context memory and frontal/executive tasks will be greater in samples of patients all of whom have frontal lesions invading the dorsolateral cortical margin.     

Neural activation during frequency-memory performance.

Lesion studies have demonstrated that frequency memory, or memory for the frequency of occurrence, is associated with prefrontal and not temporal lobe lesions. This study examined neural activation during performance on a frequency-memory-judgment task and a recognition-memory task, both using words. Relative to a control task, the authors observed peaks of activation during frequency-memory performance in the left ventrolateral prefrontal cortex (BA 45) and other areas typically associated with working memory (dorsolateral prefrontal cortex, posterior parietal cortex). Recognition performance was associated with activation in the same left ventrolateral prefrontal location as was observed with frequency memory. When comparing activation during frequency memory with activation during recognition memory, the authors found a suppression of activation in the hippocampus bilaterally during frequency memory. This study supports a neuroanatomical distinction between frequency and recognition memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A functional magnetic resonance imaging study of auditory vigilance with low and high information processing demands.

This study identified the brain activations associated with auditory vigilance tasks, using functional magnetic resonance imaging. We created auditory continuous performance tests (CPTs) in which a demanding task (working memory task) was made more difficult than a simple vigilance task by increasing working memory and interference filtering demands. Two cohorts of normal male controls performed significantly worse on the working memory CPT than on the vigilance task. Compared to the vigilance task, performance of the working memory task produced significant signal change in lateral and medial prefrontal cortex, precentral cortex, temporal lobe, including insula and hippocampus, parietal-occipital cortex, cingulate, thalamus, and superior colliculus. Performance and degree of activation was associated with an estimate of IQ. Further research should clarify the contributions of working memory and interference filtering to the activated network. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A reexamination of the concurrent discrimination learning task: The importance of anterior inferotemporal cortex, area TE.

For 30 years, the concurrent discrimination learning task has figured prominently in studies used to determine the effects of medial temporal lobe damage in monkeys. However, the findings from these studies have been contradictory. We explored the contribution to concurrent discrimination performance of inadvertent damage to area TE by reexamining the behavioral data and histological material from monkeys with medial temporal lobe lesions previously tested in our laboratory. The amount of inadvertent damage to area TE was more predictive of impaired performance on the concurrent discrimination learning task than was the amount of damage to any medial temporal lobe structure, including the perirhinal cortex. These findings resolve earlier inconsistent findings regarding the concurrent discrimination learning task by demonstrating that performance on this task depends on area TE and not on perirhinal cortex or other medial temporal lobe structures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differentiating among prefrontal substrates in psychopathy: Neuropsychological test findings.

Frontal lobe and consequent executive dysfunction have long been related to psychopathy. More recently, there have been suggestions that specific regions of frontal cortex, rather than all of frontal cortex, may be implicated in psychopathy. To examine this issue, the authors presented 25 individuals with psychopathy and 30 comparison individuals with measures preferentially indexing the orbitofrontal cortex (OFC; object alternation task), dorsolateral prefrontal cortex (DLPFC; spatial alternation task), and anterior cingulate cortex (ACC; number-Stroop reading and counting tasks). The individuals with psychopathy showed significant impairment on the measure preferentially sensitive to OFC functioning. In contrast, the 2 groups did not show impairment on the measures preferentially sensitive to the functioning of the DLPFC or ACC. These results are interpreted with reference to executive dysfunction accounts of the disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A computer-generated measure of nursing workload for the emergency department based on discharge diagnosis

Following medial temporal damage, mature humans are impaired in retaining new information over long delays but not short delays. The question of whether a similar dissociation occurs in children was addressed by testing children (ages 7-16) with unilateral temporal lobe epilepsy (TLE) and controls on short- and long-term memory tasks, including a spatial delayed response task (SDR). Early-onset TLE did not affect performance on short delays on SDR, but it did impair performance at the longest delay (60 s), similar to adults with unilateral medial temporal damage. In addition, early-onset TLE affected performance on pattern recall, spatial span, and verbal span with rehearsal interference. No differences were found on story recall or on a response inhibition task.     

Enhanced memory performance on an internal-internal source monitoring test following acute psychosocial stress.

Research on the effect of acute stress and high levels of glucocorticoids on memory has largely focused on memory tasks involving the medial temporal lobe (e.g., declarative memory). Less is known, however, about the effects of stress and glucocorticoids on more strategic memory processes regulated by the prefrontal cortex (e.g., source monitoring). In the current study, the authors investigated whether exposure to acute psychosocial stress would result in altered source monitoring performance relative to the performance of a nonstressed control group. To this end, the authors assigned nonsmoking, healthy, young men to either a stress (n = 22) or a control (n = 18) condition, after which the men were given an internal source monitoring test. Results show that relative to control participants, stressed participants made fewer source monitoring errors. This study suggests that stress may have differential effects on memory, depending on whether the memory test is regulated by the prefrontal cortex or the medial temporal lobe. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Class II correction with magnets and superelastic coils followed by straight-wire mechanotherapy. Occlusal changes during and after dental therapy

We investigated facial recognition memory (for previously unfamiliar faces) and facial expression perception with functional magnetic resonance imaging (fMRI). Eight healthy, right-handed volunteers participated. For the facial recognition task, subjects made a decision as to the familiarity of each of 50 faces (25 previously viewed; 25 novel). We detected signal increase in the right middle temporal gyrus and left prefrontal cortex during presentation of familiar faces, and in several brain regions, including bilateral posterior cingulate gyri, bilateral insulae and right middle occipital cortex during presentation of unfamiliar faces. Standard facial expressions of emotion were used as stimuli in two further tasks of facial expression perception. In the first task, subjects were presented with alternating happy and neutral faces; in the second task, subjects were presented with alternating sad and neutral faces. During presentation of happy facial expressions, we detected a signal increase predominantly in the left anterior cingulate gyrus, bilateral posterior cingulate gyri, medial frontal cortex and right supramarginal gyrus, brain regions previously implicated in visuospatial and emotion processing tasks. No brain regions showed increased signal intensity during presentation of sad facial expressions. These results provide evidence for a distinction between the neural correlates of facial recognition memory and perception of facial expression but, whilst highlighting the role of limbic structures in perception of happy facial expressions, do not allow the mapping of a distinct neural substrate for perception of sad facial expressions.     

Swelling-induced activation of Na+,K+,2Cl- cotransport in C6 glioma cells: kinetic properties and intracellular signalling mechanisms

Thirty-six children with autism, 24 children with learning difficulties (matched with the autistic group for sentence comprehension), and 41 normally-developing preschoolers were given two simple tasks: a hand-game requiring inhibitory control, and a delayed-reward situation tapping metacognitive awareness of strategies for coping with the delay period. For both clinical groups, performance on the two tasks was correlated, even when the effect of comprehension level was partialled out. However, no such correlation was observed for the preschoolers, once age was taken into account. The results are discussed in terms of potential links between executive-function and mental-state awareness.     

Effects of divided attention on temporal processing in patients with lesions of the cerebellum or frontal lobe.

Prefrontal cortex and cerebellum have both been implicated in temporal processing tasks although the exact contribution of each system remains unclear. To investigate this issue, control participants and patients with either prefrontal or cerebellar lesions were tested on temporal and nontemporal perceptual tasks under 2 levels of attentional load. Each trial involved a comparison between a standard tone and a subsequent comparison tone that varied in frequency, duration, or both. When participants had to make concurrent judgments on both dimensions, patients with frontal lobe lesions were significantly impaired on both tasks whereas the variability of cerebellar patients increased in the duration task only. This dissociation suggests that deficits on temporal processing tasks observed in frontal patients can be related to the attention demands of such tasks; cerebellar patients have a more specific problem related to timing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Short-term and long-term memory in early temporal lobe dysfunction.

Following medial temporal damage, mature humans are impaired in retaining new information over long delays but not short delays. The question of whether a similar dissociation occurs in children was addressed by testing children (ages 7-16) with unilateral temporal lobe epilepsy (TLE) and controls on short- and long-term memory tasks, including a spatial delayed response task (SDR). Early-onset TLE did not affect performance on short delays on SDR, but it did impair performance at the longest delay (60 s), similar to adults with unilateral medial temporal damage. In addition, early-onset TLE affected performance on pattern recall, spatial span, and verbal span with rehearsal interference. No differences were found on story recall or on a response inhibition task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Strategic processing and memory for temporal order in patients with frontal lobe lesions.

This study evaluated whether deficits in memory for temporal order in patients with frontal lobe lesions result from impaired automatic encoding of temporal information or are secondary to deficits in effortful processes, such as the use of organizational strategies and control of interference. Patients with lesions in the dorsolateral prefrontal cortex and control participants were tested on temporal order reconstruction of semantically related and unrelated word lists learned under intentional or incidental conditions. Memory for temporal order in patients with frontal lobe lesions was sensitive to semantic relatedness but not to intention to learn. Tests of item free recall and recognition using similar encoding manipulations indicated that order performance in these patients was dissociable from item memory. Results indicate that automatic processing of temporal information is intact in patients with frontal lobe lesions but that strategic processing of this information is impaired. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial memory deficits in patients with lesions to the right hippocampus and to the right parahippocampal cortex

Spatial memory tasks, performance of which is known to be sensitive to hippocampal lesions in the rat, or to medial temporal lesions in the human, were administered in order to investigate the effects of selective damage to medial temporal lobe structures of the human brain. The patients had undergone thermo-coagulation with a single electrode along the amygdalo-hippocampal axis in an attempt to alleviate their epilepsy. With this surgical technique, lesions to single medial temporal lobe structures can be carried out. The locations of the lesions were assessed by means of digital high-resolution magnetic resonance imaging and software allowing a 3-D reconstruction of the brain. A break in the collateral sulcus, dividing it into the anterior collateral sulcus and the posterior collateral sulcus is reported. This division may correspond to the end of the entorhinal/perirhinal cortex and the start of the parahippocampal cortex. The results confirmed the role of the right hippocampus in visuo-spatial memory tasks (object location, Rey-Osterrieth Figure with and without delay) and the left for verbal memory tasks (Rey Auditory Verbal Learning Task with delay). However, patients with lesions either to the right or to the left hippocampus were unimpaired on several memory tasks, including a spatial one, with a 30 min delay, designed to be analogous to the Morris water maze. Patients with lesions to the right parahippocampal cortex were impaired on this task with a 30 min delay, suggesting that the parahippocampal cortex itself may play an important role in spatial memory.     

Prefrontal cortex and rule abstraction: Where and whether? Theoretical comment on Moore et al. (2009).

The primate dorsolateral prefrontal cortex is implicated in diverse aspects of behavioral regulation, cognitive control, and memory. However, direct neuropsychological evidence supporting a requirement of this area in functions other than spatial working memory has been scarce. T. L. Moore, S. P. Schettler, R. J. Killiany, D. L. Rosene, and M. B. Moss (see record 2009-04037-001) have shown, for the first time, that lesions of dorsolateral prefrontal cortex in the rhesus monkey (including areas 9 and 46) substantially impair performance in a test of executive function modeled on the Wisconsin Card Sorting Task. The pattern of impairment is consistent with a role for dorsolateral prefrontal areas in rule abstraction but may relate to a role for this area in rule maintenance as well. Interestingly, monkeys with dorsolateral prefrontal lesions do not appear to perseverate in their use of particular rules in the task, different from the common impairment associated with frontal lobe damage in humans. These findings indicate that dorsolateral prefrontal cortex is necessary for some aspects of rule-guided behavior in the primate brain and help illuminate the involvement of different prefrontal areas in different aspects of executive function and rule-guided behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive deficits in parents from multiple-incidence autism families

This study compares parents of two autistic children with parents of a Down syndrome (DS) proband, on tests of intelligence, reading and spelling, and executive function. Autism parents performed significantly worse than DS parents on performance IQ, a test of executive function, and some reading measures (e.g. passage comprehension and rapid automatized naming). These results suggest that cognitive deficits may be an expression of the underlying genetic liability for autism and that these characteristics may contribute to a more broadly defined autism phenotype.     

New developments in the role of cytokines and chemokines in inflammatory myopathies

Humans are readily able to distinguish expected and unexpected sensory events. Whether a single mechanism underlies this ability is unknown. The most common type of expected sensory events are those generated as a consequence of self-generated actions. Using H2 15O PET, we studied brain responses to such predictable sensory events (tones) and to similar unpredictable events and especially how the processing of predictable sensory events is modified by the context of a causative self-generated action. Increases in activity when the tones were unpredictable were seen in the inferior and superior temporal lobe bilaterally, the right parahippocampal gyrus and right parietal cortex. Self-generated actions produced activity in a number of motor and premotor areas, including dorsolateral prefrontal cortex. We observed an interaction between the predictability of stimuli and self-generated actions in several areas, including the medial posterior cingulate cortex, left insula, dorsomedial thalamus, superior colliculus and right inferior temporal cortex. This modulation of activity associated with stimulus predictability in the context of self-generated actions implies that these areas may be involved in self-monitoring processes. Detection of expected stimuli and the detection of the sensory consequences of self-generated actions appear to be functionally distinct processes, and are carried out in different cortical areas. These observations support theoretical approaches to cognition that postulate the existence of a self-monitoring system.     

Antibodies to myelin basic protein in children with autistic behavior

Based on a possible pathological relationship of autoimmunity to autism, antibodies reactive with myelin basic protein (anti-MBP) were investigated in the sera of autistic children. Using a screening serum dilution of 1:400 in the protein-immunoblotting technique, approximately 58% (19 of 33) sera of autistic children (< or = 10 years of age) were found to be positive for anti-MBP. This result in autistics was significantly (p < or = .0001) different from the controls (8 of 88 or only 9% positive), which included age-matched children with normal health, idiopathic mental retardation (MR) and Down syndrome (DS), and normal adults of 20 to 40 years of age. Since autism is a syndrome of unknown etiology, it is possible that anti-MBP antibodies are associated with the development of autistic behavior.     

Task-related and item-related brain processes of memory retrieval

In all cognitive tasks, general task-related processes operate throughout a given task on all items, whereas specific item-related processes operate differentially on individual items. In typical functional neuroimaging experiments, these two sets of processes have usually been confounded. Herein we report a combined positron emission tomography and event-related potential (ERP) experiment that was designed to distinguish between neural correlates of task-related and item-related processes of memory retrieval. Two retrieval tasks, episodic and semantic, were crossed with episodic (old/new) and semantic (living/nonliving) properties of individual items to yield evidence of regional brain activity associated with task-related processes, item-related processes, and their interaction. The results showed that episodic retrieval task was associated with increased blood flow in right prefrontal and posterior cingulate cortex, as well as with a sustained right-frontopolar-positive ERP, but that the semantic retrieval task was associated with left frontal and temporal lobe activity. Retrieval of old items was associated with increased blood flow in the left medial temporal lobe and with a brief late positive ERP component. The results provide converging hemodynamic and electrophysiological evidence for the distinction of task- and item-related processes, show that they map onto spatially and temporally distinct patterns of brain activity, and clarify the hemispheric encoding/retrieval asymmetry (HERA) model of prefrontal encoding and retrieval asymmetry.     

Hippocampal and cortical growth-associated protein-43 messenger RNA in schizophrenia

Growth-associated protein-43 is involved in maturational and plasticity-associated processes, and changes in growth-associated protein-43 expression are a marker of altered plasticity following experimental and neuropathological lesions. Using in situ hybridization, we have investigated growth-associated protein-43 mRNA in the medial temporal lobe and cerebral cortex in 11 normal subjects and 11 matched subjects with schizophrenia, a disorder in which perturbed neurodevelopment and aberrant plasticity are implicated. In the schizophrenia group, growth-associated protein-43 messenger RNA was decreased in the medial temporal lobe, primary visual cortex and anterior cingulate gyrus, but was unaltered in the superior temporal and dorsolateral prefrontal cortices. Correlations of growth-associated protein-43 messenger RNA signal between areas were stronger and more numerous in the schizophrenics than in the controls, suggesting a more global regulation of growth-associated protein-43 expression. Finally, the ratio of growth-associated protein-43 messenger RNA to synaptophysin messenger RNA--a putative index of the production of new synapses--was decreased in the medial temporal lobe in the schizophrenics. Our findings imply that neuronal plasticity as indexed by growth-associated protein-43 expression is impaired, and perhaps aberrantly regulated, in schizophrenia. The data support the emerging view that the disease pathophysiology is one which affects the hippocampal and cortical circuitry and that the abnormalities are reflected in the altered expression of specific neuronal genes.