Molly B. Sparling

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.

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.

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.

Working memory deficits after traumatic brain injury: Catecholaminergic mechanisms and prospects for treatment - A review

Primary objective: To review the neural circuitry and neurochemistry of working memory and outline the evidence for working memory deficits after traumatic brain injury, and the evidence for the use of catecholaminergic agents in the amelioration of these deficits. Current knowledge gaps and research needs are identified. Main outcomes and results: Impairments in working memory are a core component of the cognitive deficits associated with traumatic brain injury. Recent progress in understanding the neural circuitry and neurochemistry of working memory suggests that catecholamines play a central role in the activation and regulation of working memory and thus lays a framework in which to consider the use of catecholaminergic agents (dopaminergic and alpha-2 adrenergic agonists) in the treatment of specific cognitive deficits after traumatic brain injury. Conclusions: The combined methods of cognitive neuroscience, functional brain imaging and neuropharmacology are proposed as an excellent method for studying working memory deficits. A strong rationale exists for the targeted use of catecholaminergic agonists in the treatment of working memory deficits after traumatic brain injury.

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.

Similarities and Differences in Semantic and Phonological Processing with Age Patterns of Functional MRI Activation

In this investigation, we analyzed the effect of age on fMRI activation during semantic and phonological decision tasks using wholebrain echoplanar imaging Nine righthanded healthy younger adults were compared to nine righthanded healthy older adult volunteers While undergoing fMRI scanning, subjects completed three functional MRI auditory stimulation tasks requiring semantic or phonological decisions (match/mismatch) about word pairs (category-exemplar, category-function, pseudo-word) Performance scores on these tasks did not differ between age groups The fMRI images were motion corrected, spatially normalized, and statistically analyzed for group similarities and differences using a randomeffects model For the semantic tasks, both older and younger adults showed activity within the inferior frontal gyrus (left more than right) and left superior temporal gyrus, whereas small regional age differences (younger?>?older) were found in the left inferior precentral region For the phonologic task, common areas of activation were found in the superior temporal gyrus (left more than right) Agerelated differences in the phonologic task were observed predominantly in the right angular region The results were not changed by entry of a quantitative atrophy index as a covariate These findings highlight the similarities in semantic processing across age groups and suggest that global age related atrophy is not impacting activation significantly in healthy older adults