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Biomedical subjects

L A Flashman

Publications and source records attributed to L A Flashman.

At least 19 recordsLinked to original sources
PubMed2003

Sex differences in semantic language processing: a functional MRI study.

Predictions based on two models of sex differences in cerebral organization of language were compared by examining fMRI patterns of 10 females and 9 males during a semantic processing task. Both groups displayed activation of left inferior frontal gyrus (IFG), left superior temporal gyrus (STG), and cingulate. Females, but not males, showed bilateral IFG and STG activation. Further analyses revealed females had less diffuse left activation and greater right posterior temporal and insula region activation than males. Results support both an interhemispheric and an intrahemispheric model of sex differences in language, suggesting that the models may not be mutually exclusive.

Brain↗
PubMed2001

Differential working memory load effects after mild traumatic brain injury.

The objective of this study was to explore the effects of increasing working memory (WM) processing load on previously observed abnormalities in activation of WM circuitry shortly after mild traumatic brain injury (MTBI). Brain activation patterns in response to increasing WM processing load (auditory n-back: 0-, 1-, 2-, and 3-back conditions) were assessed with fMRI in 18 MTBI patients within 1 month of their injury and in 12 healthy controls. Performance accuracy on these tasks was also measured. Brain activation patterns differed between MTBI patients and controls in response to increasing WM processing loads. Controls maintained their ability to increase activation in regions of WM circuitry with each increase in WM processing load. MTBI patients showed disproportionately increased activation during the moderate processing load condition, but very little increase in activation associated with the highest processing load condition. Task performance did not differ significantly between groups on any task condition. MTBI patients showed a different pattern of allocation of processing resources associated with a high processing load condition compared to healthy controls, despite similar task performance. This suggests that injury-related changes in ability to activate or modulate WM processing resources might underlie some of the memory complaints after MTBI.

Adolescent↗
PubMed2001

Deep brain stimulation in neuropsychiatric disorders.

Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus, subthalamic nucleus, and internal globus pallidus has been put forth as an alternative to surgical ablation for the treatment of movement disorders. In this paper, the authors discuss the history and putative physiologic mechanisms underlying DBS of these target regions. The authors then review empirical findings pertaining to the effects of DBS on neurological symptoms, cognitive functioning, and psychiatric symptoms in Parkinson's disease and essential tremor, the disorders for which the procedure has been most extensively applied. Finally, emerging and potential novel areas of application of DBS for the treatment of neuropsychiatric disorders and symptoms are discussed.

Brain↗
PubMed2001

Brain activation on fMRI and verbal memory ability: functional neuroanatomic correlates of CVLT performance.

We have recently reported (Saykin et al., 1999b) selective activation of left medial temporal lobe structures during processing of novel compared to familiar words using functional magnetic resonance imaging (fMRI). The current study describes the relationship between a widely used clinical test of verbal learning, the California Verbal Learning Test (CVLT), and the previously reported fMRI activations. Thirteen right-handed healthy adult participants were studied with whole brain echo-planar fMRI while listening to novel and recently learned (familiar) words intermixed pseudorandomly in an event-related design. These participants were also tested with the CVLT. Scores for CVLT Trial 1 (immediate encoding of novel words) and recognition discriminability (recognition of familiar vs. novel words) were correlated with fMRI signal change during processing of novel versus familiar words using a covariance model implemented in SPM96. For the novel words analysis, voxels in the right anterior hippocampus correlated significantly with Trial 1 (r = .76 at the maxima). For the recognition analysis, a significant cluster of voxels was found in the right dorsolateral prefrontal cortex (r = .88 at the maxima). Our prior results of separable left medial temporal activation to novel and familiar words, together with results of the covariance analyses reported here, suggest that in addition to the left medial temporal lobe (MTL) regions that are engaged during novel and familiar word processing, the right hippocampus and right frontal lobe are also involved, particularly in those participants with better memory ability. This positive relationship between fMRI activation and CVLT performance suggests a role for these right hemisphere regions in successful memory processing of verbal material, perhaps reflecting more efficient encoding and retrieval strategies that facilitate memory.

Adult↗
PubMed2001

Effects of retroactive and proactive interference on word list recall in schizophrenia.

Schizophrenia spectrum patients (N = 143) and healthy controls (N = 160) were administered the Rey Auditory Verbal Learning Test (RAVLT) and tests of executive functioning to directly investigate the effects of proactive interference (PI) and retroactive interference (RI) on word list recall. It was hypothesized that by virtue of the predicted preferential association between executive functioning and RI (relative to PI), patients would demonstrate increased susceptibility to RI in their ability to recall word lists. Results indicated that patients show increased susceptibility to RI relative to PI. Furthermore, this difference appeared to be related to the frontally-mediated central executive functions that were preferentially associated with RI but not PI susceptibility.

Adult↗
PubMed2001

Neuroimaging findings in mild traumatic brain injury.

The role of neuroimaging in the diagnosis and management of mild traumatic brain injury (TBI) is evolving. In general, the structural imaging techniques play a role in acute diagnosis and management, while the functional imaging techniques show promise for clarification of pathophysiology, symptom genesis, and mechanisms of recovery. A wide array of neuropathological processes are involved in mild TBI including changes in bone (e.g., a skull fracture), tissue density and water content (edema), blood flow, white matter integrity and pathway connectivity (diffuse axonal injury), and subtle changes in the neuronal and extracellular biochemical milieu. No single imaging technique is capable of addressing all these processes. It is, therefore, important to be aware of the advantages and limitations of the various available imaging modalities. This paper selectively reviews the pertinent literature on the structural and functional imaging in mild TBI.

Brain↗
PubMed2000

The relationship between fMRI activation and cerebral atrophy: comparison of normal aging and alzheimer disease.

Functional MRI has recently been used to examine activation associated with aging and dementia, yet little is known regarding the effect of cerebral atrophy on fMRI signal. The purpose of this study was to examine the relationship between measures of global and regionally specific atrophy and fMRI activation in normal aging and in Alzheimer disease (AD). Two groups of subjects were studied with echoplanar imaging and quantitative structural volumetry: healthy controls spanning a broad age and atrophy range (n = 16) and patients with mild AD (n = 8). Results from a semantic task previously found to activate left inferior frontal (LIFG) and left superior temporal (LSTG) gyri were analyzed. The correlations between clusters of activation in the LIFG and LSTG and measures of local atrophy in the LIFG and LSTG regions were evaluated. For control subjects, there was no significant correlation between activation and regional or total brain atrophy (for LIFG r = -0.03, NS; for LSTG r = 0.20, NS). In contrast, for AD patients, there was a significant positive correlation between atrophy and activation in LIFG (r = 0.70, P = 0.05) but not LSTG (r = 0.00, NS). These results suggest that activation of language regions and atrophy within those regions may be independent among healthy adults spanning a broad age and atrophy range. However, in AD, a relationship exists in the LIFG that may reflect compensatory recruitment of cortical units or disease-specific changes in the hemodynamic response.

Adult↗
PubMed2000

Smaller brain size associated with unawareness of illness in patients with schizophrenia.

OBJECTIVE: Although several neuropsychological studies have supported the notion of frontal and parietal lobe involvement in unawareness of illness in schizophrenia, neuroanatomic differences have not been examined. METHOD: Thirty patients with schizophrenia spectrum disorder were rated by means of a structured interview assessing awareness of illness and performance on clinical rating scales. With 13 healthy comparison subjects, they underwent neuropsychological assessment and a scan using three-dimensional, spoiled gradient recall acquisition volumetric magnetic resonance imaging. RESULTS: Patients who were relatively unaware of their illness had smaller brain and intracranial volumes (brain tissue plus CSF) than either aware patients or normal comparison subjects, who did not differ significantly from each other. CONCLUSIONS: These findings suggest that unawareness of illness is an important phenomenological feature with neurological correlates that is seen in at least one subgroup of patients with schizophrenia.

Adult↗
PubMed2000

Cognitive correlates of the negative, disorganized, and psychotic symptom dimensions of schizophrenia.

Knowledge of the relationship between specific cognitive abnormalities and the clinical symptoms of schizophrenia could give insight into the nature of their underlying pathophysiology. Composite scores were generated for negative, disorganized, and psychotic symptom ratings in 134 patients with schizophrenia (DSM-IV criteria). Partial correlations (each composite corrected for the others) were computed with neuropsychological measures. Negative symptoms were related to poor performance on tests of verbal learning and memory, verbal fluency, visual memory, and visual-motor sequencing. Disorganized symptoms were correlated with lower verbal IQ and poor concept attainment. Psychotic symptoms had no significant relationship with cognitive deficit.

Adult↗
PubMed1999

Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study.

OBJECTIVE: To assess patterns of regional brain activation in response to varying working memory loads shortly after mild traumatic brain injury (MTBI). BACKGROUND: Many individuals complain of memory difficulty shortly after MTBI. Memory performance in these individuals can be normal despite these complaints. METHODS: Brain activation patterns in response to a working memory task (auditory n-back) were assessed with functional MRI in 12 MTBI patients within 1 month of their injury and in 11 healthy control subjects. RESULTS: Brain activation patterns differed between MTBI patients and control subjects in response to increasing working memory processing loads. Maximum intensity projections of statistical parametric maps in control subjects showed bifrontal and biparietal activation in response to a low processing load, with little additional increase in activation associated with the high load task. MTBI patients showed some activation during the low processing load task but significantly increased activation during the high load condition, particularly in the right parietal and right dorsolateral frontal regions. Task performance did not differ significantly between groups. CONCLUSION: MTBI patients differed from control subjects in activation pattern of working memory circuitry in response to different processing loads, despite similar task performance. This suggests that injury-related changes in ability to activate or to modulate working memory processing resources may underlie some of the memory complaints after MTBI.

Adult↗
PubMed1999

Neuroanatomic substrates of semantic memory impairment in Alzheimer's disease: patterns of functional MRI activation.

Impairment in semantic processing occurs early in Alzheimer's disease (AD) and differential impact on subtypes of semantic relations have been reported, yet there is little data on the neuroanatomic basis of these deficits. Patients with mild AD and healthy controls underwent 3 functional MRI auditory stimulation tasks requiring semantic or phonological decisions (match-mismatch) about word pairs (category-exemplar, category-function, pseudoword). Patients showed a significant performance deficit only on the exemplar task. On voxel-based fMRI activation analyses, controls showed a clear activation focus in the left superior temporal gyrus for the phonological task; patients showed additional foci in the left dorsolateral prefrontal and bilateral cingulate areas. On the semantic tasks, predominant activation foci were seen in the inferior and middle frontal gyrus (left greater than right) in both groups but patients showed additional activation suggesting compensatory recruitment of locally expanded foci and remote regions, for example, right frontal activation during the exemplar task. Covariance analyses indicated that exemplar task performance was strongly related to signal increase in bilateral medial prefrontal cortex. The authors conclude that fMRI can reveal similarities and differences in functional neuroanatomical processing of semantic and phonological information in mild AD compared to healthy elderly, and can help to bridge cognitive and neural investigations of the integrity of semantic networks in AD.

Aged↗
PubMed1999

Functional differentiation of medial temporal and frontal regions involved in processing novel and familiar words: an fMRI study.

Results of recent functional magnetic resonance imaging (fMRI) studies of memory are not entirely consistent with lesion studies. Furthermore, although imaging probes have identified neural systems associated with processing novel visual episodic information, auditory verbal memory using a novel/familiar paradigm has not yet been examined. To address this gap, fMRI was used to compare the haemodynamic response when listening to recently learned and novel words. Sixteen healthy adults (6 male, 10 female) learned a 10-item word list to 100% criterion, approximately 1 h before functional scanning. During echo-planar imaging, subjects passively listened to a string of words presented at 6-s intervals. Previously learned words were interspersed pseudo-randomly between novel words. Mean scans corresponding to each word type were analysed with a random-effects model using statistical parametric mapping (SPM96). Familiar (learned) words activated the right prefrontal cortex, posterior left parahippocampal gyrus, left medial parietal cortex and right superior temporal gyrus. Novel words activated the anterior left hippocampal region. The results for the familiar words were similar to those found in other functional imaging studies of recognition and retrieval and implicate the right dorsolateral prefrontal and left posterior medial temporal lobe (MTL) regions. The results for novel words require replication, but are consistent with the substantial lesion and PET literature implicating the anterior MTL as a critical site for processing novel episodic information, presumably to permit encoding. Together, these results provide evidence for an anterior-posterior functional differentiation within the MTL in processing novel and familiar verbal information. The differentiation of MTL functions that was obtained is consistent with a large body of PET activation studies but is unique among fMRI studies, which to date have differed from results with PET. Further, the finding of left MTL lateralization is consistent with lesion-based material-specific models of memory.

Adult↗
PubMed1998

Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study.

BACKGROUND: Although many quantitative magnetic resonance imaging studies have found significant volume reductions in the hippocampi of patients with schizophrenia compared with those of normal control subjects, others have not. Therefore, the issue of hippocampal volume differences associated with schizophrenia remains in question. METHODS: Two meta-analyses were conducted to reduce the potential effects of sampling error and methodological differences in data acquisition and analysis. Eighteen studies with a total patient number of 522 and a total control number of 426 met the initial selection criteria. RESULTS: Meta-analysis 1 yielded mean effect sizes of 0.37 (P<.001) for the left hippocampus and 0.39 (P<.001) for the right, corresponding to a bilateral reduction of 4%. Meta-analysis 2 indicated that the inclusion of the amygdala in the region of interest significantly increased effect sizes across studies (effect size for the left hippocampus and amygdala, 0.67; for the right, 0.72), whereas variables such as illness duration, total slice width, magnet strength, the use of the intracranial volume as a covariate, measurement reliability, and study quality did not. No laterality differences were observed in these data. CONCLUSIONS: Schizophrenia is associated with a bilateral volumetric reduction of the hippocampus and probably of the amygdala as well. These findings reinforce the importance of the medial temporal region in schizophrenia and are consistent with frequently reported memory deficits in these patients. Future quantitative magnetic resonance imaging studies evaluating the hippocampal volume should measure the hippocampus and amygdala separately and compare the volumetric reduction in these structures to that observed in other gray matter areas.

Adult↗
PubMed1997

Lack of an association between delayed memory and hippocampal and temporal lobe size in patients with schizophrenia and healthy controls.

The purpose of the present study was to investigate putative neural substrates of long-term (delayed) memory in schizophrenia and young healthy controls. Ten "low" and 10 "high" memory patients were selected from a large sample of DSM-III-R diagnosed schizophrenia spectrum patients, based on composite verbal and nonverbal delayed recall memory scores. Ten "low" and 9 "high" memory individuals were also selected from a larger sample of young healthy controls. Magnetic resonance imaging scans were acquired on a 1.5-T GE Signa scanner using a SPGR sequence (repetition time = 24 msec, echo time = 5 msec). Hippocampal volumes were computed from manual tracings (intraclass correlation = .96), and temporal lobe and whole brain tissue volumes were obtained using a semiautomated technique. In both the patient sample and controls, there was no significant relationship between delayed memory ability and hippocampal, temporal lobe, or whole brain volume. The integration of results from this study, and from studies on normal aging and Alzheimer's disease, supports a model suggesting that hippocampal size may be an indicator of long-term memory ability, but only when hippocampal measures reflect aging and degenerative hippocampal atrophy. If the hippocampal measures reflect individual differences in hippocampal size prior to the onset of hippocampal atrophy, then hippocampal size does not appear to predict long-term memory ability.

Adult↗
PubMed1996

Temporal lobe epilepsy and performance on the Wisconsin Card Sorting Test.

The replicability of previous evidence for differential performance between left and right temporal lobe epileptic patients on the Wisconsin Card Sorting Test (WCST) was evaluated in a new sample of candidates for focal resection. Many subjects obtained high scores on indices of perseveration, which are commonly thought to reflect frontal dysfunction, but there were no differences in performance between patients with language-dominant and nondominant temporal foci. The findings confirm existing evidence that performance decrements on the WCST can be associated with epileptic foci and focal lesions in nonfrontal brain lesions.

Adult↗
PubMed1996

Soft signs and neuropsychological performance in schizophrenia.

OBJECTIVE: Both neuropsychological impairment and neurological soft signs have been documented in at least a subset of patients with schizophrenia. The purpose of the present study was to examine the relationship between soft signs and neuropsychological performance in patients with schizophrenia in order to address the issue of whether soft signs are related to global or more selective cognitive impairment. METHOD: Patients with a DSM-III-R diagnosis of schizophrenia (N=176) were given a standardized neuropsychological battery and underwent a neurological examination. The study group was dichotomized on the basis of presence or absence of neurological soft signs. RESULTS: Patients with neurological soft signs (N=68) demonstrated significantly poorer performance on neuropsychological tasks that assessed timed motor speed and motor coordination (e.g., finger tapping, the Purdue Pegboard task, and part B of the Trail Making Test). These findings continued to be significant even after lifetime medication exposure, extrapyramidal symptoms, and abnormal involuntary movements were used as covariates. CONCLUSIONS: These findings support the notion that soft signs are a manifestation of a localizable behavioral deficit of the systems that are involved in motor speed, coordination, and sequencing and are not indicative of global cognitive impairment. The specific deficit in motor abilities is consistent with the types of neurological soft signs that are most frequently reported and suggests involvement of frontal/subcortical circuitry in schizophrenia.

Adolescent↗
PubMed1986

The effects of chronic desmethylimipramine on entorhinal cortical kindling in rats.

Chronic pretreatment of rats with desmethylimipramine (DMI) significantly slowed the rate of seizure generalization elicited by repeated electrical stimulation of the entorhinal cortex (kindling). An identical drug regimen administered to either fully kindled rats or rats partially kindled to early motor seizure stages failed to significantly alter kindling profiles in these animals. Under these latter conditions, in fact, there was a tendency for chronic DMI to exacerbate seizure activity. The effect of chronic DMI pretreatment to slow the development of kindled seizure generalization did not occur if a two-week delay was interposed between the end of drug treatment and the beginning of kindling trials. Results suggest that the retardation of entorhinal cortical kindling rate is dependent on DMI-induced CNS adaptations which recover within two weeks following treatment, and this effect is dependent on the presence of DMI-induced adaptations in a naive (unkindled) nervous system. Alterations of either the kindled state or the adaptational state produced by chronic drug eliminate the slowing of seizure generalization observed when both conditions are present.

Animals↗