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Use of Anomalous Sentences Repetition Test (ASRT) in 16 patients with diagnosis of dementia of Alzheimer's type, 16 normal elderly and 18 patients with depression revealed no difference in the age adjusted scores between the three groups, suggesting that it is not a good test for diagnosing dementia or differentiating dementia from depression.
BACKGROUND: Major depression is associated with cognitive deficits, particularly those requiring central executive functioning. Depressed patients also tend to focus on and think about their symptoms and problems ("ruminate") more than non-depressed controls. Although an association has been found between rumination and impaired performance on a central executive processing task, the causal relation between impaired executive functioning and rumination has not been determined. This study sought to directly manipulate rumination and assess the impact on executive functioning in depression as measured by random number generation. METHODS: Depressed patients (n=14) and non-depressed controls (n=14) were compared on a random number generation task, performed after both a rumination induction and after a distraction induction, with order of inductions counter balanced within each group. RESULTS: Compared with the distraction induction, the rumination induction produced a significant increase in both ruminations and the tendency towards stereotyped counting responses (thought to reflect a failure of inhibitory executive control) in depressed patients but not in controls. However, after distraction, no difference in random number generation or rumination was found between the two groups. CONCLUSIONS: The aspects of executive function involved in random number generation are not fundamentally impaired in depressed patients. In depressed patients, the rumination induction seems to trigger the continued generation of ruminative stimulus independent thoughts, which interferes with concurrent executive processing.
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During reaching, the brain may rely on internal models to transform desired sensory outcomes into motor commands. This transformation depends on both the state of the limb and the cues that can identify the context of the movement. How are contextual cues and information about state of the limb combined in the computations of internal models? We considered a reaching task where forces on the hand depended on both the direction of movement (state of the limb) and order of that movement in a predefined sequence (contextual cue). When the cue was available, the motor system formed an internal model that used both serial order and target direction to program motor commands. Assuming that the internal model was formed by a population code through a combination of unknown basis elements, the sensitivity of the bases with respect to state of the limb and contextual cue should dictate how error in one type of movement affected all other movement types. Using a state-space theory, we estimated this generalization function and identified the adaptive system from trial-by-trial changes in performance. The results implied that the basis elements were tuned to direction of movement but output of each basis at its preferred direction was multiplicatively modulated by a weak tuning with respect to the contextual cue. Activity fields that multiplicatively encode diverse sources of information may serve as a general mechanism for a single network to produce context-dependent motor output.
Object-selective cortical regions exhibit a decreased response when an object stimulus is repeated [repetition suppression (RS)]. RS is often associated with priming: reduced response times and increased accuracy for repeated stimuli. It is unknown whether RS reflects stimulus-specific repetition, the associated changes in response time, or the combination of the two. To address this question, we performed a rapid event-related functional MRI (fMRI) study in which we measured BOLD signal in object-selective cortex, as well as object recognition performance, while we manipulated stimulus repetition. Our design allowed us to examine separately the roles of response time and repetition in explaining RS. We found that repetition played a robust role in explaining RS: repeated trials produced weaker BOLD responses than nonrepeated trials, even when comparing trials with matched response times. In contrast, response time played a weak role in explaining RS when repetition was controlled for: it explained BOLD responses only for one region of interest (ROI) and one experimental condition. Thus repetition suppression seems to be mostly driven by repetition rather than performance changes. We further examined whether RS reflects processes occurring at the same time as recognition or after recognition by manipulating stimulus presentation duration. In one experiment, durations were longer than required for recognition (2 s), whereas in a second experiment, durations were close to the minimum time required for recognition (85-101 ms). We found significant RS for brief presentations (albeit with a reduced magnitude), which again persisted when controlling for performance. This suggests a substantial amount of RS occurs during recognition.
To study the prefrontal neuronal mechanism for the encoding and mnemonic processing of multiple objects, the order of object presentation, and the retrieval of an object among objects in the working memory, we recorded neuronal activity from the lateral prefrontal cortex while two monkeys performed the serial probe reproduction task. In the task, two objects (C1 and C2) were presented sequentially interleaved with a delay (D1) period, and after the second delay (D2) period, a color cue was presented. Monkeys were trained to select one target object on the basis of the color stimulus. During the C1 and C2 periods, we found responses that depended on the order of presentation (order-selective response). During the D1 and/or D2 periods, two-thirds of the neurons with object-selective delay-period activity showed order-selective activity coding either C1 or C2. Neurons with larger response magnitudes during the C2 period showed order-selective delay-period activity during the D2 period. These order-selective responses during the C2 period could also contribute to order-selective delay-period activity, and order-selective delay-period activity during the D1 and D2 periods could play an essential role in storing information on both the object and the temporal order of presentation. During the color cue period, two-thirds of the neurons with responses showed target object selectivity (CT and T responses), although the target object was not presented during this period. The CT and T responses could play a critical role in the retrieval of an item among various items in the working memory.
BACKGROUND: The aim of the present study was to analyse serial position effects for immediate and delayed free recall in patients with dementia of the Alzheimer type and controls. EXPERIMENT 1: 44 patients with dementia of the Alzheimer-type and 24 non-demented controls were asked for immediate and delayed free recall of 12 schematic drawings of common objects presented at the rate of 10 s/picture. Steep primacy effects were obtained at all delays in controls. By contrast, primacy effects were significantly impaired in patients with dementia at all delays of recall. Small immediate and delayed recall recency effects were found in both, patients and controls. EXPERIMENT 2: 19 patients with dementia of the Alzheimer type and 21 controls were asked for immediate and delayed free picture recall with presentation rates of 10, 5 and 1 s/picture. Again, primacy effects were significantly impaired in demented patients versus controls. With shorter presentation times, immediate recall recency effects were more pronounced than with longer presentation times, and no delayed recall recency effects were found. CONCLUSIONS: Primacy effect is impaired for immediate and delayed recall in dementia of the Alzheimer type. By contrast, immediate recall recency effect and possibly also long-term recency effect are preserved. The loss of the primacy effect contributes to the impairment of episodic memory in dementia of the Alzheimer type. Therefore further research is warranted into pharmacological and psychological interventions that might re-establish the primacy effect. Possibly, the orientation of demented patients might be improved by psychological techniques that rely on long-term recency effect.
In the Third National Health and Nutrition Examination Survey (NHANES III), three measures of cognitive function [Simple Reaction Time Test (SRTT), Symbol Digit Substitution Test (SDST), and Serial Digit Learning Test (SDLT)] were administered to a half-sample of 3,385 adult men and nonpregnant women 30-59 years of age with no history of stroke. We used multiple linear regression analysis to determine whether there was an independent association between performance on each cognitive function measure and defined hypertension (HTN) alone, type 2 diabetes mellitus (DM) alone, and coexistent HTN and DM after adjustment for demographic and socioeconomic variables and selected health behaviors. After adjustment for the sociodemographic variables, the combination of HTN + DM, but not HTN alone or DM alone, was significantly associated with worse performance on the SRTT (p = 0.031) and the SDST (p = 0.011). A similar pattern was observed for SDLT performance, but the relationship did not reach statistical significance (p = 0.101). We conclude that HTN in combination with DM is associated with detectable cognitive decrements in persons under age 60.
It is established that recall of an item from a list of sequentially presented items is sensitive to the item's position in the memorized list. However, little is known about the brain mechanisms that mediate these serial position effects. Studies of working memory retrieval using event-related potentials report amplitude reductions during retrieval (auditory cortical N100, neocortical late positive wave [LPW]) as memory load increases. We tested the hypothesis that N100 and LPW amplitudes to probes are also affected by serial position. Event-related potentials were recorded from subjects performing an auditory working memory task. A set of one or five digits was memorized, then subjects classified a probe digit as either present or absent from the memory set. A control task was also given. Amplitudes of the N100 and LPW were reduced in the 5-item versus the 1-item set. In the 5-item set N100 amplitude was significantly larger for the initial (1st) serial position, relative to Positions 2-5, while linear increases in LPW amplitude were seen across serial positions (5th > 1st position). A control task without memorization showed no N100 or LPW amplitude changes with set size or serial position. The findings reveal that the N100 and LPW are influenced differently by serial position during working memory retrieval: N100 shows a primacy effect and LPW demonstrates a recency effect. The results suggest that primacy and recency effects may be mediated by different brain regions at different times during memory retrieval.
OBJECTIVE: In an exploration of the schizophrenia spectrum, the authors compared thalamic size, shape, and metabolic activity in unmedicated patients with schizophrenia and schizotypal personality disorder to findings in age- and sex-matched healthy control subjects. METHOD: Coregistered magnetic resonance imaging (MRI) and positron emission tomography scans were obtained in 27 schizophrenic patients, 13 patients with schizotypal personality disorder, and 32 control subjects who performed a serial verbal learning test during tracer uptake. After thalamus edges were outlined on 1.2-mm MRI scans, a radial warping program yielded significance probability mapping in three dimensions. RESULTS: Significance probability mapping (with resampling) identified an area in the region of the mediodorsal nucleus bilaterally with significantly lower relative metabolism in the schizophrenia group than in either the control or schizotypal personality disorder groups, which did not differ from each other. The three groups did not differ significantly in total thalamic volume in square millimeters or thalamic volume relative to brain volume. Shape analyses revealed that schizophrenic patients had significantly fewer pixels in the left anterior region, whereas patients with schizotypal personality disorder had significantly fewer pixels in the region of the right mediodorsal nucleus than did control subjects. CONCLUSIONS: Schizophrenic patients showed significant metabolism and shape differences from control subjects in selective subregions of the thalamus, whereas patients with schizotypal personality disorder showed only a difference in shape. Because the mediodorsal and anterior nuclei have different connections with limbic and prefrontal structures, the anterior thalamic shrinkage and mediodorsal metabolic and shape changes might relate to the different clinical pictures in schizotypal personality disorder and schizophrenia.
OBJECTIVE: In patients with autism, behavioral deficits as well as neuroimaging studies of the anterior cingulate cortex suggest ventral rather than dorsal striatal and thalamic abnormalities in structure and function. The authors used imaging studies to map volumetric and metabolic differences within the entire dorsoventral extent of the striatum and thalamus. METHOD: Magnetic resonance imaging (MRI) and positron emission tomography (PET) were used to measure volumes and metabolic activity in the thalamus, caudate, and putamen in 17 patients with autism or Asperger's disorder and 17 age- and sex-matched comparison subjects. Subjects performed a serial verbal learning test during the [(18)F]-fluorodeoxyglucose uptake period. The regions of interest were outlined on contiguous axial MRI slices. After PET/MRI coregistration, region-of-interest coordinates were applied to the PET scan for each individual. Between-group differences in metabolism were assessed by three-dimensional statistical probability mapping. RESULTS: The patients with autism spectrum disorders had greater volumes of the right caudate nucleus than comparison subjects as well as a reversal of the expected left-greater-than-right hemispheric asymmetry. Patients also had lower relative glucose metabolic rates bilaterally in the ventral caudate, putamen, and thalamus. Patients with autism had lower metabolic activity in the ventral thalamus than those with Asperger's disorder, but they did not differ from comparison subjects in metabolic activity in the caudate nucleus. CONCLUSIONS: These results are consistent with a deficit in the anterior cingulate-ventral striatum-anterior thalamic pathway in patients with autism spectrum disorders. The results also suggest an important role for the caudate in helping support working-memory demands.
OBJECTIVE: Few previous studies have investigated the association between APOE genotype and brain activation during performance of cognitive tasks in healthy middle-aged and elderly subjects, and the results have been mixed. The authors investigated APOE-mediated differential brain activation in a group of healthy elderly subjects. METHODS: Using H215O positron emission tomography (PET), they imaged 32 healthy subjects (26 non-epsilon4 carriers and 6 epsilon4 carriers) performing a serial shape-recognition memory task under two conditions: Simple Demand (SD), in which one shape was presented in each study trial, and Titrated Demand (TD), in which study list length was adjusted so that each subject recognized words at approximately 75% accuracy. Multiple-regression analyses were performed, with the "activation" difference (TD-SD PET counts) as the dependent variable and the APOE genotype (presence versus absence of the epsilon4 allele) as the independent variable. RESULTS: Compared with non-carriers, epsilon4 carriers exhibited significantly decreased TD-SD activation differences in the left superior temporal, right superior frontal, left postcental, left precuneus, and posterior cingulate gyrus because epsilon4 carriers (versus non-carriers) showed increased activation during the SD and decreased activation during the TD condition. CONCLUSION: Patterns of brain activation during a nonverbal memory task differed as a function of APOE genotype and, therefore, of genetic risk for Alzheimer disease (AD). Differences in activation were not a reflection of task difficulty, but indicate memory-related altered cognitive processing. Brain regions with decreased activation in the epsilon4 subjects may result from subclinical incipient AD pathology and/or APOE-related neurophysiologic heterogeneity.
OBJECTIVE: Cytoarchitectonic changes in the anterior cingulate cortex, hippocampus, subiculum, entorhinal cortex, amygdala, mammillary bodies, and septum were reported in a postmortem study of autism. Previously, the authors found smaller cingulate volume and decreased metabolism of the cingulate in seven autistic patients. In this study, they measured the volume and glucose metabolism of the amygdala, hippocampus, and cingulate gyrus in an expanded group of 17 patients with autism spectrum disorders (autism [N=10] or Asperger's disorder [N=7]) and 17 age- and sex-matched healthy volunteers. METHOD: Subjects performed a serial verbal learning test during (18)F-deoxyglucose uptake. The amygdala, hippocampus, and cingulate gyrus were outlined on magnetic resonance imaging scans, volumes of the structures were applied to matching coregistered positron emission tomography scans, and three-dimensional significance probability mapping was performed. RESULTS: Significant metabolic reductions in both the anterior and posterior cingulate gyri were visualized in the patients with autism spectrum disorders. Both Asperger's and autism patients had relative glucose hypometabolism in the anterior and posterior cingulate as confirmed by analysis of variance; regional differences were also found with three-dimensional significance probability mapping. No group differences were found in either the metabolism or the volume of the amygdala or the hippocampus. However, patients with autism spectrum disorders showed reduced volume of the right anterior cingulate gyrus, specifically in Brodmann's area 24'. CONCLUSIONS: Compared with age- and sex-matched healthy volunteers, patients with autism spectrum disorders showed significantly decreased metabolism in both the anterior and posterior cingulate gyri.
OBJECTIVE: The authors' goal was to determine whether patients with bipolar II disorder had altered regional brain responses to novel motor sequences. METHOD: Regional cerebral blood flow was measured with positron emission tomography in 13 patients with bipolar II disorder and 14 healthy comparison subjects. Participants performed a serial reaction time task in which they were visually cued to press one of four buttons at a time. The order of button presses was determined by a complex sequence that was changed in the latter half of the study. RESULTS: In the comparison subjects a spatial attention circuit in the superior parietal lobe and supplementary motor area was activated in response to the introduction of the new sequence. Patients did not display this activation pattern; instead, a widespread limbic network was activated in response to the new sequence. CONCLUSIONS: The attentional resources of patients with bipolar II disorder are not reallocated when they are confronted with a nonemotional motor task; rather, their performance is altered through activation of limbic circuitry.
OBJECTIVE: During object manipulation, grip force must be adjusted in anticipation of destabilizing load forces to prevent the object from slipping. This study used three gripping tasks to assess whether schizophrenia affects the predictive mechanisms required for the scaling, timing, and/or sequencing of motor actions. METHOD: Sixteen patients with schizophrenia and 16 comparison subjects matched for age, sex, and educational level 1) lifted objects of various mass and texture (lift task) and 2) used a manipulandum to hit (hit task) or resist (resist task) impacts produced by a collision with a pendulum. For an optimized performance, all tasks demanded a predictive increase in grip force and the timing of external events. The fluid sequencing of finger and hand submovements was required for the lift and the hit tasks but not for the resist task. RESULTS: Patients were impaired in the smooth execution of both the lift and the hit tasks but not in the performance of the resist task. In all three tasks, the scaling of grip force was similar for patients and comparison subjects. CONCLUSIONS: Schizophrenia is associated with a specific deficit in the sequencing of motor actions rather than with an overall problem in the predictive control of movement.
The authors hypothesized that older depressed patients would perform more poorly on the Ascending Digits Task (ADT) when matched against a nondepressed elderly comparison group. In a novel measure, the ADT, 129 older depressives scored more poorly than 129 comparison subjects in bivariate analyses and models controlling for demographic variables. The ADT may be a good measure of executive function in older adults.
This study characterized memory functions in geriatric schizophrenic inpatients with a battery of memory tests sensitive to neuropsychological impairments in either temporal or frontal brain regions. In patients clinically rated as cognitively impaired (n = 24), nearly all of these measures showed deficits relative to less impaired patients (n = 25). Factor analysis found consistent correlations between the tests and their putative cortical localization. Discriminant analysis suggested the pattern of impairments was not consistent with a generalized deficit. These results introduce the possibility, to be directly tested with neuropathological study, that the severe cognitive deficits in elderly schizophrenic patients are due to dysfunctions in either the temporal or frontal regions of the cerebral cortex, with the specific type of dysfunction varying across cases.