Biomedical subjects

Gregory G Brown

Publications and source records attributed to Gregory G Brown.

At least 19 recordsLinked to original sources

PubMed2006

The neural correlates of habituation of response to startling tactile stimuli presented in a functional magnetic resonance imaging environment.

Functional magnetic resonance imaging (fMRI) provides a means of identifying neural circuitry associated with startle and its modulation in humans. Twelve subjects who demonstrated eyeblink startle in the laboratory were recruited for an fMRI study in which they were scanned while presented with two identical runs consisting of alternating blocks of no stimuli and startling tactile stimuli. Together, behavioral and imaging data are consistent with a pattern of general cortical and thalamic activation induced by startling stimuli that shows habituation both across and within runs. From Run 1 to Run 2, both the eyeblink amplitude and the fMRI signal decreased. Within Run 1, there was a graded decrease in eyeblink amplitude and whole-brain fMRI signal across blocks of startling stimuli. A similar graded decrease was observed in the thalamus signal, as well. Thus, startling tactile stimuli initially induce widespread cortical and thalamic activity, perhaps mediated by the reticular activating system. The activity then habituates in a graded fashion with repeated presentations of the stimuli.

Adult↗

PubMed2006

Amygdala reactivity and mood-congruent memory in individuals at risk for depressive relapse.

BACKGROUND: According to cognitive diathesis-stress theories, a latent cognitive vulnerability to depression is activated by negative affect in individuals at risk for depressive relapse. This vulnerability can manifest as mood-congruent memory during sad mood and may involve amygdala response, which is implicated in memory for emotionally arousing stimuli. This study examined whether amygdala modulates memory for negatively valenced words before and after a sad mood induction in healthy individuals with and without a history of recurrent major depression. METHODS: Fourteen unmedicated remitted depressed (RD) and 14 matched never depressed (ND) individuals were scanned using functional magnetic resonance imaging (fMRI) while performing a self-referent encoding/evaluation task (SRET) preceding and following a sad mood challenge. After each SRET, participants' free recall was assessed. RESULTS: Following sad mood induction, bilateral amygdala response during encoding of valenced words predicted increased recall of negative self-referent words for a subset of RD participants. This association was not present before the sad mood induction and was not evident in individuals without a history of depression, regardless of mood state. CONCLUSIONS: These results are consistent with cognitive diathesis-stress theories and suggest a role for the amygdala in modulating mood-congruent memory during transient sad mood in individuals who are vulnerable to depression relapse.

Adult↗

PubMed2006

Improved anatomic delineation of the antidepressant response to partial sleep deprivation in medial frontal cortex using perfusion-weighted functional MRI.

This study used functional magnetic resonance imaging (fMRI) to clarify the sites of brain activity associated with the antidepressant effects of sleep deprivation (SD). We hypothesized: 1) depressed responders' baseline ventral anterior cingulate (AC) perfusion will be greater than that of nonresponders and controls; 2) following partial sleep deprivation (PSD), ventral AC perfusion will significantly decrease in responders only. Seventeen unmedicated outpatients with current major depression and eight controls received perfusion-weighted fMRI and structural MRI at baseline and following 1 night of late-night PSD. Talairach-transformed gray matter masks were merged with Talairach Daemon-based region of interest (ROI) templates. Baseline left ventral AC (LVAC) perfusion was greater in responders than nonresponders. There was no difference involving the medial frontal cortex. Responders' LVAC perfusion dropped from baseline to PSD scans compared with nonresponders and controls, as did perfusion in the right dorsal AC. In the patient group as a whole, decrease in LVAC perfusion from baseline to PSD scans correlated directly with the decrease in the modified 17-item Hamilton Depression Rating Scale (HDRS17) between baseline and PSD conditions. These data--the first using fMRI--show greater anatomic specificity than previous findings of SD and depression in linking decreased brain activity in this area with clinical improvement.

Adolescent↗

PubMed2006

Striatopallidal regulation of affect in bipolar disorder.

BACKGROUND: Evidence from the neuroimaging literature suggests that the basal ganglia plays an important role in the regulation of affect. This conclusion stems almost exclusively from group comparisons and it remains unclear whether previous findings can be confirmed from a longitudinal study of mood change. The aim of this study was to increase our understanding of the functional role of the basal ganglia and thalamus in relation to change in affect in patients with bipolar disorder. METHODS: Ten bipolar disorder subjects participated in a functional MRI study. We used a simple motor reaction time task to probe subcortical regions bilaterally. Subjects were scanned twice, once when their self-reported mood ratings indicated hypomania or euthymia and then again when they were in depressed states. RESULTS: Subjects in their euthymic or hypomanic states exhibited increased caudate activity bilaterally and the globus pallidus of the left hemisphere. Longitudinal analyses revealed a significant association between an increase in severity of depression and a decrease in activity in the external segment of the right globus pallidus. CONCLUSIONS: Our findings suggest that the globus pallidus is less responsive during a simple motor task in the depressed compared to the normal or euthymic states in patients with bipolar disorder. These results are consistent with current physiologic models of basal ganglia circuitry in which an increase in caudate activity results in an increase in inhibitory GABAergic outflow to the external globus pallidus and subsequent decrease in thalamocortical excitation and may underlie the clinical manifestations of depression in bipolar disorder. LIMITATIONS: The findings of this study need to be interpreted with caution as correlation coefficients may be overestimated in this small study sample.

Adult↗

PubMed2006

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response.

Previous studies of episodic memory report a greater extent of blood-oxygenation-level-dependent (BOLD) response in non-demented older adults with the apolipoprotein E epsilon-4 (APOE epsilon4) allele than in those without the allele. We conducted a functional MRI study to investigate whether APOE genotype is related to brain response to verbal paired-associate encoding and consolidation, particularly in the right hemisphere, among non-demented older adults. Structurally segmented volumes and BOLD response were measured in 13 non-epsilon4 and 12 epsilon4 subjects. The epsilon4 group displayed greater activation than the non-epsilon4 group in multiple right hemisphere regions for previously encoded word pairs relative to fixation. Activation within manually outlined hippocampal regions of interest also displayed genotype-specific dissociations consistent with whole brain analyses. Furthermore, this differential BOLD response occurred in the presence of equivalent behavioral and neuropsychological performances as well as comparable hippocampal and overall structural segmentation volumes between groups. Results implicate a widely distributed and interconnected network of right hemisphere brain regions that may be involved in compensating for APOE epsilon4-related deficiencies associated with verbal episodic memory encoding and consolidation.

Aged↗

PubMed2006

Quantitative evaluation of automated skull-stripping methods applied to contemporary and legacy images: effects of diagnosis, bias correction, and slice location.

Performance of automated methods to isolate brain from nonbrain tissues in magnetic resonance (MR) structural images may be influenced by MR signal inhomogeneities, type of MR image set, regional anatomy, and age and diagnosis of subjects studied. The present study compared the performance of four methods: Brain Extraction Tool (BET; Smith [2002]: Hum Brain Mapp 17:143-155); 3dIntracranial (Ward [1999] Milwaukee: Biophysics Research Institute, Medical College of Wisconsin; in AFNI); a Hybrid Watershed algorithm (HWA, Segonne et al. [2004] Neuroimage 22:1060-1075; in FreeSurfer); and Brain Surface Extractor (BSE, Sandor and Leahy [1997] IEEE Trans Med Imag 16:41-54; Shattuck et al. [2001] Neuroimage 13:856-876) to manually stripped images. The methods were applied to uncorrected and bias-corrected datasets; Legacy and Contemporary T1-weighted image sets; and four diagnostic groups (depressed, Alzheimer's, young and elderly control). To provide a criterion for outcome assessment, two experts manually stripped six sagittal sections for each dataset in locations where brain and nonbrain tissue are difficult to distinguish. Methods were compared on Jaccard similarity coefficients, Hausdorff distances, and an Expectation-Maximization algorithm. Methods tended to perform better on contemporary datasets; bias correction did not significantly improve method performance. Mesial sections were most difficult for all methods. Although AD image sets were most difficult to strip, HWA and BSE were more robust across diagnostic groups compared with 3dIntracranial and BET. With respect to specificity, BSE tended to perform best across all groups, whereas HWA was more sensitive than other methods. The results of this study may direct users towards a method appropriate to their T1-weighted datasets and improve the efficiency of processing for large, multisite neuroimaging studies.

Adult↗

PubMed2006

Diazepam-induced prospective memory impairment and its relation to retrospective memory, attention, and arousal.

The amnestic effects of benzodiazepines are well documented on a variety of memory tasks. However, prospective memory (PM), or remembering to execute an action at a future time, has not been studied previously. This study examined the effect of diazepam on word list recall, PM, sustained attention, and subjective ratings of arousal. Forty-eight healthy participants, aged 19-35, received an average of 0.19 mg/kg oral diazepam or placebo in a double-blind manner. Retrospective memory and PM were assessed by free recall of unrelated word lists and by instructing participants to request a hidden belonging at the end of the session, respectively. Sustained attention was measured by multiple trials of a digit cancellation task, and subjective arousal was assessed by self-ratings of drowsiness. Diazepam impaired performance on all measures, including PM. Reduced PM performance was associated with decreased subjective arousal in the diazepam group but was unrelated to sustained attention. This is the first report of the effects of benzodiazepines on prospective remembering, and further supports the view that the arousal/attentional system is composed of partially independent subsystems that have differential relationships to memory.

Adult↗

PubMed2006

Towards positional cloning in Brassica napus: generation and analysis of doubled haploid B. rapa possessing the B. napus pol CMS and Rfp nuclear restorer gene.

The Polima (pol) system of cytoplasmic male sterility (CMS) and its fertility restorer gene Rfp are used in hybrid rapeseed production in Brassica napus. To facilitate map-based cloning of the Rfp gene, we have successfully transferred the pol cytoplasm and Rfp from the amphidiploid B. napus to the diploid species B. rapa and generated a doubled haploid pol cytoplasm B. rapa population that segregates for the Rfp gene. This was achieved through interspecific crosses, in vitro rescue of hybrid embryos, backcrosses, and microspore culture. Male fertility conditioned by Rfp was shown to co-segregate in this population with Rfp-specific mitochondrial transcript modifications and with DNA markers previously shown to be linked to Rfp in B. napus. The selfed-progeny of one doubled haploid plant were confirmed to be characteristic B. rapa diploids by cytogenetic analysis. Clones recovered from a genomic library derived from this plant line using the RFLP probe cRF1 fell into several distinct physical contigs, one of which contained Rfp-linked polymorphic restriction fragments detected by this probe. This indicates that chromosomal DNA segments anchored in the Rfp region can be recovered from this library and that the library may therefore prove to be a useful resource for the eventual isolation of the Rfp gene.

Brassica napus↗

PubMed2006

The impact of sleep deprivation and task difficulty on networks of fMRI brain response.

Previous fMRI research has found altered brain response after total sleep deprivation (TSD), with TSD effects moderated by task difficulty. Specific models of the impact of sleep deprivation and task difficulty on brain response have yet to be developed. Differences in networks of fMRI measured brain response during verbal encoding in sleep deprived and well-rested individuals were examined with structural equation modeling (SEM). During fMRI scanning, 23 healthy volunteers memorized words either easy or difficult to recall, 12 (well-rested) and 36 hours (sleep deprived) after awaking. A priori models that linked specified regions of interest were evaluated, with the focus on the extent to which two left parietal regions interacted with the left inferior frontal gyrus (Model 1) or with the right inferior frontal gyrus (Model 2). Task difficulty, not TSD, determined which model fit the brain response data; Model 2 fit best for hard words before and after TSD, whereas Model 1 fit best for easy words. TSD altered the patterns of interaction within each of the best fitting models: prefrontal interactions with the left inferior parietal lobe were diminished and intra-parietal interactions increased. Sleep deprivation and item difficulty produce different effects on brain networks involved in verbal learning.

Adult↗

PubMed2005

Does amygdalar perfusion correlate with antidepressant response to partial sleep deprivation in major depression?

This study used functional MRI (fMRI) to clarify the sites of brain activity associated with the antidepressant effects of sleep deprivation (SD). We hypothesized: (1) baseline perfusion in right and left amygdalae will be greater in responders than in nonresponders; (2) following partial sleep deprivation (PSD), perfusion in responders' right and left amygdalae would decrease. Seventeen unmedicated outpatients with current major depression and eight controls received perfusion-weighted fMRI and structural MRI at baseline and following 1 night of late-night PSD. Baseline bilateral amygdalar perfusion was greater in responders than nonresponders. Clusters involving both amygdalae decreased from baseline to PSD specifically in responders. Right amygdalar perfusion diverged with PSD, increasing in nonresponders and decreasing in responders. These novel amygdalar findings are consistent with the overarousal hypothesis of SD as well as other functional imaging studies showing increased baseline amygdalar activity in depression and decreased amygdalar activity with remission or antidepressant medications.

Adolescent↗

PubMed2005

Compensatory recruitment after sleep deprivation and the relationship with performance.

This study examined the effects of total sleep deprivation (TSD) on cerebral responses to a verbal learning task with two levels of word difficulty. A total of 32 subjects were studied with functional magnetic resonance imaging (FMRI) after normal sleep and following 36 h of TSD. Cerebral responses to EASY words were identical on both nights, but several brain regions showed increased activation to HARD words following TSD compared with following a normal night of sleep (NORM). These regions included bilateral inferior frontal gyrus, bilateral dorsolateral prefrontal cortex, and bilateral inferior parietal lobe. Better free recall performance on the HARD words after TSD was related to increased cerebral responses within the left inferior and superior parietal lobes and left inferior frontal gyrus. Recall was negatively related to activation within the right inferior frontal gyrus. Overall, the findings support the predictions of the compensatory recruitment hypothesis that task demands influence both the likelihood and location of increased cerebral activation during task performance following TSD, and refine that hypothesis by identifying a specific task demand that plays a role. The performance relationships suggest increased activation may be both beneficial (compensatory) and interfere with task performance, depending on the brain regions involved.

Adult↗

PubMed2005

fMRI response to spatial working memory in adolescents with comorbid marijuana and alcohol use disorders.

Alcohol and marijuana use are prevalent in adolescence, yet the neural impact of concomitant use remains unclear. We previously demonstrated functional magnetic resonance imaging (fMRI) response to spatial working memory (SWM) among teens with alcohol use disorders (AUD) compared to controls, and predicted that adolescents with marijuana and alcohol use disorders would show additional abnormalities. Participants were three groups of 15-17-year-olds: 19 non-abusing controls, 15 AUD teens with limited exposure to drugs, and 15 teens with comorbid marijuana and alcohol use disorders (MAUD) and minimal other drug experience. After >2 days' abstinence, participants performed a SWM task during fMRI acquisition. fMRI brain response patterns differed between groups, despite similar performance on the task. MAUD youths showed less activation in inferior frontal and temporal regions than controls, and more response in other prefrontal regions. Compared to AUD teens, MAUD youths also showed less inferior frontal and temporal activation, but more medial frontal response. Overall, MAUD youths showed different brain response abnormalities than teens with AUD alone, despite relatively short histories of substance involvement. This pattern could suggest compensation for marijuana-related attention and working memory deficits. However, relatively recent use and premorbid features may influence results, and should be examined in future studies.

Adolescent↗

PubMed2005

fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease.

OBJECTIVE: To determine whether APOE genotype influences brain response and whether nonverbal stimuli generate findings comparable with those of previous studies that used verbal stimuli. The relationship between APOE genotype and blood oxygenation level dependent (BOLD) brain response was examined during a picture-encoding task in nondemented older adults. METHODS: Twenty nondemented participants with normal episodic memory function were divided into two groups based on the presence (n = 10) or absence (n = 10) of the APOE epsilon4 allele. Picture learning was completed during functional MRI in a blocked design alternating between experimental (novel pictures) and control (repeated picture) conditions. RESULTS: Nondemented older adults with an APOE epsilon4 allele showed greater magnitude and extent of BOLD brain response during learning of new pictures relative to their matched epsilon3 counterparts. Different patterns and directions of association between hippocampal activity and learning and memory performance were also demonstrated. CONCLUSIONS: The results suggest that brain response differences are not due to poorer general memory abilities, differential atrophy, or brain response during control conditions, but instead appear to be directly influenced by APOE genotype. Results are consistent with a compensatory hypothesis wherein older adults at genetic risk for Alzheimer disease by virtue of the APOE epsilon4 allele appear to require additional cognitive effort to achieve comparable performance levels on tests of episodic memory encoding.

Adaptation, Psychological↗

PubMed2005

Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors.

Nucleoside reverse transcriptase inhibitors (NRTIs) suppress human immunodeficiency virus (HIV) replication, but are often associated with mitochondrial toxicity. Although well studied outside of the central nervous system, no investigation has examined the effects of these drugs on brain mitochondria of individuals living with HIV. The authors used proton magnetic resonance spectroscopy to evaluate NRTI-related changes in brain mitochondria. N-acetylaspartate (NAA; sensitive to alterations in mitochondrial integrity) was measured in frontal lobe white and gray matter of 18 HIV+ individuals taking didanosine and/or stavudine (two NRTIs likely to cause mitochondrial toxicity), 14 HIV+ individuals taking zidovudine and lamivudine, 16 HIV+ individuals not currently taking antiretrovirals, and 17 HIV- controls. The HIV+ groups were comparable on demographic measures, estimates of illness severity, and estimated length of HIV infection. Those taking didanosine and/or stavudine had a significant 11.4% decrease in concentrations of frontal white matter NAA compared to HIV- controls, whereas NAA levels of the other HIV+ groups were intermediate. Group differences in metabolites were not found in frontal gray matter. Lower levels of frontal white matter NAA were associated with longer periods of didanosine and/or stavudine treatment (r = -.41, P = .06). Levels of NAA were not related to length of zidovudine/lamivudine treatment (r = -.04, P = .44). Furthermore, taking more than one of stavudine, didanosine, and abacavir increased the likelihood of having reduced NAA. The results are consistent with previous studies finding HIV-related changes in neuronal integrity. However, because NRTIs can injure mitochondria, we propose that the observed reductions in NAA in individuals taking didanosine and/or stavudine may be the result of depleted brain mitochondria and/or alterations in cellular respiration. Measurement of brain metabolites sensitive to impairments in energy metabolism, including NAA, may aid in early detection of subclinical NRTI-mediated mitochondrial toxicity.

Adult↗

PubMed2005

Cell-specific regulation of a Brassica napus CMS-associated gene by a nuclear restorer with related effects on a floral homeotic gene promoter.

Cytoplasmic male sterility (CMS) is a maternally inherited defect in pollen production specified by novel mitochondrial genes. It can be suppressed by nuclear restorer (Rf) genes which normally downregulate expression of a CMS-associated novel mitochondrial gene. Two forms of Brassica napus CMS, nap and pol, are associated with related chimeric genes, orf222 and orf224, respectively. We show that in pol and nap CMS, anther locule development is asynchronous and asymmetric, that one or more locules within each anther may fail to develop entirely and that CMS anthers display polarity in locule development. We show, by in situ hybridization, that orf222 transcripts accumulate in sterile anthers prior to development of morphological differences between CMS and restored stamens, and remain preferentially localized to microsporangia. In fertility-restored anthers, however, orf222 transcript levels remain low throughout development. Some sporogenous and meiotic cells differentiate within CMS anthers and form functional pollen despite retaining high orf222 transcript levels, suggesting that the effect of orf222 expression in blocking pollen development is limited to an early and specific stage. Transcripts of other mitochondrial genes, exemplified by atp6 and cob, and of the nuclear-encoded ATP synthase gamma subunit, accumulate preferentially in the microsporangia of both sterile and fertile anthers. Thus nuclear fertility restoration reduces orf222 transcript levels in a gene and tissue-specific manner. We observe differences between CMS and fertile plants in the timing and patterning of APETALA3 promoter activity that suggest a possible basis for the developmental abnormalities of CMS flowers.

Brassica napus↗

PubMed2005

Reproducibility of functional MR imaging: preliminary results of prospective multi-institutional study performed by Biomedical Informatics Research Network.

PURPOSE: To prospectively investigate the factors--including subject, brain hemisphere, study site, field strength, imaging unit vendor, imaging run, and examination visit--affecting the reproducibility of functional magnetic resonance (MR) imaging activations based on a repeated sensory-motor (SM) task. MATERIALS AND METHODS: The institutional review boards of all participating sites approved this HIPAA-compliant study. All subjects gave informed consent. Functional MR imaging data were repeatedly acquired from five healthy men aged 20-29 years who performed the same SM task at 10 sites. Five 1.5-T MR imaging units, four 3.0-T units, and one 4.0-T unit were used. The subjects performed bilateral finger tapping on button boxes with a 3-Hz audio cue and a reversing checkerboard. In a block design, 15-second epochs of alternating baseline and tasks yielded 85 acquisitions per run. Functional MR images were acquired with block-design echo-planar or spiral gradient-echo sequences. Brain activation maps standardized in a unit-sphere for the left and right hemispheres of each subject were constructed. Areas under the receiver operating characteristic curve, intraclass correlation coefficients, multiple regression analysis, and paired Student t tests were used for statistical analyses. RESULTS: Significant factors were subject (P < .005), k-space (P < .005), and field strength (P = .02) for sensitivity and subject (P = .03) and k-space (P = .05) for specificity. At 1.5-T MR imaging, mean sensitivities ranged from 7% to 32% and mean specificities were higher than 99%. At 3.0 T, mean sensitivities and specificities ranged from 42% to 85% and from 96% to 99%, respectively. At 4.0 T, mean sensitivities and specificities ranged from 41% to 73% and from 95% to 99%, respectively. Mean areas under the receiver operating characteristic curve (+/- their standard errors) were 0.77 +/- 0.05 at 1.5 T, 0.90 +/- 0.09 at 3.0 T, and 0.95 +/- 0.02 at 4.0 T, with significant differences between the 1.5- and 3.0-T examinations and between the 1.5- and 4.0-T examinations (P < .01 for both comparisons). Intraclass correlation coefficients ranged from 0.49 to 0.71. CONCLUSION: MR imaging at 3.0- and 4.0-T yielded higher reproducibility across sites and significantly better results than 1.5-T imaging. The effects of subject, k-space, and field strength on examination reproducibility were significant.

Adult↗

PubMed2004

Spatial working memory among middle-aged and older patients with schizophrenia and volunteers using fMRI.

OBJECTIVE: Goldman-Rakic and Selemon (Schizophr. Bull. 23 (1997)) hypothesized that many of the symptoms of schizophrenia can be explained by deficits of working memory (WM) that are, in turn, caused by dysfunction of dorsolateral prefrontal cortex (DLPFC). We examined whether older patients with schizophrenia would show an aberrant neural response in the DLPFC or other brain sites when performing a spatial working memory (WM) task adapted from McCarthy et al. (Proc. Natl. Acad. Sci. U. S. A. 91 (1994)). METHOD: Middle-aged and older patients with schizophrenia or schizoaffective disorder and healthy volunteers performed a spatial WM task contrasted with two baselines, passive and active viewing (PV and AV, respectively), while blood oxygen level dependent (BOLD) images were acquired in a functional magnetic resonance study. RESULTS: Patients did not perform significantly less well on the spatial tasks compared to the volunteers. Although we found no significant group effects in spatial WM activation of DLPFC, we did observe areas in medial frontal cortex including the left anterior cingulate gyrus, parietal areas of the both hemispheres, multiple sites within the basal ganglia of the left hemisphere, and the left superior temporal gyrus where healthy volunteers showed greater BOLD response to WM. In a second pattern, patients showed a greater BOLD response to WM in left fusiform gyrus [Brodmann's Area (BA) 19], peri-rolandic areas, medial frontal area; right anterior cerebellum (culmen), middle occipital lobe, and postcentral/supramarginal gyri (BA 2/40). CONCLUSIONS: Middle-aged and older patients with schizophrenia display normal or near-normal spatial WM activation of DLPFC when the processing demands of the WM task are within their performance capacity. Nonetheless, even when patients perform nearly normally, they demonstrate an aberrant pattern of brain response.

Age Factors↗

PubMed2004

Increasing task difficulty facilitates the cerebral compensatory response to total sleep deprivation.

STUDY OBJECTIVES: To test the role of task difficulty in the cerebral compensatory response after total sleep deprivation (TSD). DESIGN: Subjects performed a modified version of Baddeley's logical reasoning task while undergoing functional magnetic resonance imaging twice: once after normal sleep and once following 35 hours of TSD. The task was modified to parametrically manipulate task difficulty. SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: 16 young adults (7 women; mean age, 27.6 +/- 6.1 years; education, 15.4 +/- 1.8 years) were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Behaviorally, subjects performed the same after TSD as while well rested. Neuroimaging data revealed a linear increase in cerebral response with a linear increase in task demands in several brain regions after normal sleep. Even stronger linear responses were found after TSD in several brain regions, including bilateral inferior parietal lobes, bilateral temporal cortex, and left inferior and dorsolateral prefrontal cortex. CONCLUSIONS: Task difficulty facilitates the cerebral compensatory response observed following TSD. Compensation manifests as both new regions that did not show significant responses to task demands in the well-rested condition, as well as stronger responses within regions typically underlying task performance. The possible significance of these 2 types of responses should be explored further, as should the importance of the parietal lobes for cognitive performance after TSD.

Adult↗