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Biomedical subjects

A J Saykin

Publications and source records attributed to A J Saykin.

At least 19 recordsLinked to original sources
PubMed2006

Regional brain atrophy in cognitively intact adults with a single APOE epsilon4 allele.

OBJECTIVE: To determine whether cognitively intact adults with the APOE epsilon3/epsilon4 genotype show reduced gray matter density on voxel-based morphometry (VBM) vs those homozygous for the epsilon3 allele. METHODS: Participants were healthy, cognitively intact, right-handed adults, age 19 to 80, who completed genotyping, neuropsychological testing, and MRI. Forty-nine participants had the epsilon3/epsilon3 genotype and 27 had the epsilon3/epsilon4 genotype. Gray matter data were analyzed using the general linear model as implemented in the Statistical Parametric Mapping package, adjusting for age and sex. RESULTS: The epsilon3/epsilon4 participants showed lower gray matter density than the epsilon3/epsilon3 participants in right medial temporal and bilateral frontotemporal regions as well as other areas. There were no regions in which epsilon3/epsilon4 participants showed higher gray matter density than epsilon3/epsilon3 participants. CONCLUSIONS: Regionally reduced gray matter density is detectable in cognitively intact adults with a single copy of the APOE epsilon4 allele.

Adult↗
PubMed2006

Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI.

OBJECTIVE: To examine the neural basis of cognitive complaints in healthy older adults in the absence of memory impairment and to determine whether there are medial temporal lobe (MTL) gray matter (GM) changes as reported in Alzheimer disease (AD) and amnestic mild cognitive impairment (MCI). METHODS: Participants were 40 euthymic individuals with cognitive complaints (CCs) who had normal neuropsychological test performance. The authors compared their structural brain MRI scans to those of 40 patients with amnestic MCI and 40 healthy controls (HCs) using voxel-based morphometry and hippocampal volume analysis. RESULTS: The CC and MCI groups showed similar patterns of decreased GM relative to the HC group on whole brain analysis, with differences evident in the MTL, frontotemporal, and other neocortical regions. The degree of GM loss was associated with extent of both memory complaints and performance deficits. Manually segmented hippocampal volumes, adjusted for age and intracranial volume, were significantly reduced only in the MCI group, with the CC group showing an intermediate level. CONCLUSIONS: Cognitive complaints in older adults may indicate underlying neurodegenerative changes even when unaccompanied by deficits on formal testing. The cognitive complaint group may represent a pre-mild cognitive impairment stage and may provide an earlier therapeutic opportunity than mild cognitive impairment. MRI analysis approaches incorporating signal intensity may have greater sensitivity in early preclinical stages than volumetric methods.

Aged↗
PubMed2004

Brain activation patterns associated with working memory in relapsing-remitting MS.

BACKGROUND: Patients with multiple sclerosis (MS) show changes in brain activation patterns during visual and motor tasks that include decreases in the typical local network for a function and increases in other brain regions. OBJECTIVE: To determine whether brain activation patterns associated with working memory are affected by MS. METHODS: Activation of working memory circuitry was examined using an fMRI n-back task in adults with mild relapsing-remitting MS (RRMS; n = 10) and demographically matched healthy controls (n = 10). RESULTS: Group differences in brain activation emerged during both low- and high-demand conditions (p < 0.001). Overall, patients showed less activation than controls in core prefrontal and parietal regions of working memory circuitry, and greater activation in other regions within and beyond typical working memory circuitry, including bilateral medial frontal, cingulate, parietal, bilateral middle temporal, and occipital regions. CONCLUSIONS: Relative to controls, patients with mild RRMS showed shifts in brain activation patterns within and beyond typical components of working memory circuitry.

Adult↗
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↗
PubMed2003

Chronic deep brain stimulation for the treatment of tremor in multiple sclerosis: review and case reports.

BACKGROUND: Deep brain stimulation (DBS) offers a non-ablative alternative to thalamotomy for the surgical treatment of medically refractory tremor in multiple sclerosis. However, relatively few outcomes have been reported. OBJECTIVE: To provide a systematic review of the published cases of DBS use in multiple sclerosis and to present four additional patients. METHODS: Quantitative and qualitative review of the published reports and description of a case series from one centre. RESULTS: In the majority of reported cases (n=75), the surgical target for DBS implantation was the ventrointeromedial nucleus of the thalamus. Tremor reduction and improvement in daily functioning were achieved in most patients, with 87.7% experiencing at least some sustained improvement in tremor control postsurgery. Effects on daily functioning were less consistently assessed across studies; in papers reporting relevant data, 76.0% of patients experienced improvement in daily functioning. Adverse effects were similar to those reported for DBS in other patient populations. CONCLUSIONS: Few of the studies reviewed used highly standardised quantitative outcome measures, and follow up periods were generally one year or less. Nonetheless, the data suggest that chronic DBS often produces improved tremor control in multiple sclerosis. Complete cessation of tremor is not necessarily achieved, there are cases in which tremor control decreases over time, and frequent reprogramming appears to be necessary.

Adult↗
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

The neuropsychology of multiple sclerosis: contributions of neuroimaging research.

Multiple sclerosis (MS) is often associated with cognitive and emotional changes that affect daily activities and quality of life. Deficits in memory, executive function, processing speed, and other cognitive domains are frequently reported. In addition, mood disturbances and fatigue are common. In this article, the authors highlight research on individual differences in the neuropsychology of MS, and emphasize neuroimaging studies that help elucidate the basis of the deficits.

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

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↗
PubMed2001

Injection of air bubbles during flushing of angiocatheters: an in vitro trial of conventional hardware and techniques.

BACKGROUND AND PURPOSE: Injected air bubbles are a well-accepted cause of stroke during cerebral angiography. We used an in vitro model to determine the frequency of occurrence of air emboli during catheter flushing using conventional hardware and techniques. METHODS: Two experimental models were used in this study. The first incorporated an in-line bubble trap. Ten members of our angiography section flushed this system in their usual fashion and then with two modifications of the hardware. The trap was inspected after each trial of seven injections and any visible bubble was measured with calipers. The second model used a peristaltic pump along with a transcranial Doppler device to look at the relative number of bubble events with modifications of the flush solution or technique. RESULTS: The closed-flush set in common usage in our department caused an increase in the number of visible bubbles in the trap as compared with an open basin. Degassing the solution and delaying injection decreased the number of bubble events noted in model 2. CONCLUSION: Bubble emboli are commonplace during flushing of angiography catheters when using conventional techniques and equipment.

Aged↗
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↗
PubMed1999

Functional MRI localisation of central nervous system regions associated with volitional inspiration in humans.

1. Functional magnetic resonance imaging (fMRI) provides a means of studying neuronal circuits that control respiratory muscles in humans with better spatial and temporal resolution than in previous positron emission tomography (PET) studies. 2. Whole brain blood oxygenation level-dependent (BOLD) changes determined by fMRI were used to identify areas of neuronal activation associated with volitional inspiration in five healthy men. Four series of scans of each subject were acquired during voluntary breathing (active task) and mechanical ventilation (passive task). Ventilation and end-tidal PCO2 were similar between tasks. Scan data were re-aligned to correct for movement artefacts and cross-referenced breath by breath to respiratory data for selective averaging of inspiratory and expiratory images. 3. Group analysis identified significant increases in the fMRI signal with volitional inspiration in the superior motor cortex, premotor cortex and supplementary motor area at loci similar to those detected in earlier studies that used PET. Additional regions activated by volitional inspiration included inferolateral sensorimotor cortex, prefrontal cortex and striatum (these foci were only revealed by PET under significant inspiratory load). 4. This study represents the first synchronised breath-by-breath analysis of respiratory-related neuronal activity with whole brain imaging in humans. Temporal resolution is sufficient to distinguish individual breaths at a normal breathing frequency.

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↗