Neural activation for actual and imagined movement following unilateral hand transplantation: a case study.

Transplantation of a donor hand has been successful as a surgical treatment following amputation, but little is known regarding the brain mechanisms contributing to the recovery of motor function. We report functional magnetic resonance imaging (fMRI) findings for neural activation related to actual and imagined movement, for a 54-year-old male patient, who had received a donor hand transplant 50 years following amputation. Two assessments, conducted 3 months and 6 months post-operatively, demonstrate engagement of motor-control related brain regions for the transplanted hand, during both actual and imagined movement of the fingers. The intact hand exhibited a more intense and focused pattern of activation for actual movement relative to imagined movement, whereas activation for the transplanted hand was more widely distributed and did not clearly differentiate actual and imagined movement. However, the spatial overlap of actual-movement and imagined-movement voxels, for the transplanted hand, did increase over time to a level comparable to that of the intact hand. At these relatively early post-operative assessments, brain regions outside of the canonical motor-control networks appear to be supporting movement of the transplanted hand.

Task-related changes in degree centrality and local coherence of the posterior cingulate cortex after major cardiac surgery in older adults.

OBJECTIVES: Older adults often display postoperative cognitive decline (POCD) after surgery, yet it is unclear to what extent functional connectivity (FC) alterations may underlie these deficits. We examined for postoperative voxel-wise FC changes in response to increased working memory load demands in cardiac surgery patients and nonsurgical controls. EXPERIMENTAL DESIGN: Older cardiac surgery patients (n = 25) completed a verbal N-back working memory task during MRI scanning and cognitive testing before and 6 weeks after surgery; nonsurgical controls with cardiac disease (n = 26) underwent these assessments at identical time intervals. We measured postoperative changes in degree centrality, the number of edges attached to a brain node, and local coherence, the temporal homogeneity of regional functional correlations, using voxel-wise graph theory-based FC metrics. Group × time differences were evaluated in these FC metrics associated with increased N-back working memory load (2-back > 1-back), using a two-stage partitioned variance, mixed ANCOVA. PRINCIPAL OBSERVATIONS: Cardiac surgery patients demonstrated postoperative working memory load-related degree centrality increases in the left dorsal posterior cingulate cortex (dPCC; p < .001, cluster p-FWE < .05). The dPCC also showed a postoperative increase in working memory load-associated local coherence (p < .001, cluster p-FWE < .05). dPCC degree centrality and local coherence increases were inversely associated with global cognitive change in surgery patients (p < .01), but not in controls. CONCLUSIONS: Cardiac surgery patients showed postoperative increases in working memory load-associated degree centrality and local coherence of the dPCC that were inversely associated with postoperative global cognitive outcomes and independent of perioperative cerebrovascular damage.

Changes in Brain Resting-state Functional Connectivity Associated with Peripheral Nerve Block: A Pilot Study.

BACKGROUND: Limited information exists on the effects of temporary functional deafferentation (TFD) on brain activity after peripheral nerve block (PNB) in healthy humans. Increasingly, resting-state functional connectivity (RSFC) is being used to study brain activity and organization. The purpose of this study was to test the hypothesis that TFD through PNB will influence changes in RSFC plasticity in central sensorimotor functional brain networks in healthy human participants. METHODS: The authors achieved TFD using a supraclavicular PNB model with 10 healthy human participants undergoing functional connectivity magnetic resonance imaging before PNB, during active PNB, and during PNB recovery. RSFC differences among study conditions were determined by multiple-comparison-corrected (false discovery rate-corrected P value less than 0.05) random-effects, between-condition, and seed-to-voxel analyses using the left and right manual motor regions. RESULTS: The results of this pilot study demonstrated disruption of interhemispheric left-to-right manual motor region RSFC (e.g., mean Fisher-transformed z [effect size] at pre-PNB 1.05 vs. 0.55 during PNB) but preservation of intrahemispheric RSFC of these regions during PNB. Additionally, there was increased RSFC between the left motor region of interest (PNB-affected area) and bilateral higher order visual cortex regions after clinical PNB resolution (e.g., Fisher z between left motor region of interest and right and left lingual gyrus regions during PNB, -0.1 and -0.6 vs. 0.22 and 0.18 after PNB resolution, respectively). CONCLUSIONS: This pilot study provides evidence that PNB has features consistent with other models of deafferentation, making it a potentially useful approach to investigate brain plasticity. The findings provide insight into RSFC of sensorimotor functional brain networks during PNB and PNB recovery and support modulation of the sensory-motor integration feedback loop as a mechanism for explaining the behavioral correlates of peripherally induced TFD through PNB.

Multisensory conflict modulates the spread of visual attention across a multisensory object.

Spatial attention to a visual stimulus that occurs synchronously with a task-irrelevant sound from a different location can lead to increased activity not only in the visual cortex, but also the auditory cortex, apparently reflecting the object-related spreading of attention across both space and modality (Busse et al., 2005). The processing of stimulus conflict, including multisensory stimulus conflict, is known to activate the anterior cingulate cortex (ACC), but the interactive influence on the sensory cortices remains relatively unexamined. Here we used fMRI to examine whether the multisensory spread of visual attention across the sensory cortices previously observed will be modulated by whether there is conceptual or object-related conflict between the relevant visual and irrelevant auditory inputs. Subjects visually attended to one of two lateralized visual letter-streams while synchronously occurring, task-irrelevant, letter sounds were presented centrally, which could be either congruent or incongruent with the visual letters. We observed significant enhancements for incongruent versus congruent letter-sound combinations in the ACC and in the contralateral visual cortex when the visual component was attended, presumably reflecting the conflict detection and the need for boosted attention to the visual stimulus during incongruent trials. In the auditory cortices, activity increased bilaterally if the spatially discordant auditory stimulation was incongruent, but only in the left, language-dominant side when congruent. We conclude that a conflicting incongruent sound, even when task-irrelevant, distracts more strongly than a congruent one, leading to greater capture of attention. This greater capture of attention in turn results in increased activity in the auditory cortex.

Longitudinal Changes in Regional Cerebral Perfusion and Cognition After Cardiac Operation.

BACKGROUND: Cardiac operation has been associated with increased risk of postoperative cognitive decline, as well as dementia risk in the general population. Few studies, however, have examined the impact of coronary revascularization or valve replacement or repair operation on longitudinal cerebral perfusion changes or their association with cognitive function. METHODS: We examined longitudinal changes in cerebral perfusion among 54 individuals with cardiac disease; 27 undergoing cardiac operation and 27 matched control patients. Arterial spin labeling magnetic resonance perfusion imaging was used to quantify cerebral blood flow within the anterior communicating artery, middle cerebral artery (MCA), and posterior communicating artery vascular territories before operation and postoperatively at 6 weeks and 1 year. Cognitive performance was examined during the same intervals by using a battery of tests that tapped memory, executive, information processing and upper extremity motor functions. Repeated measures, mixed models were used to examine for perfusion changes and the association between perfusion changes and cognition. RESULTS: Significant postoperative increases in perfusion were observed at 6 weeks within the MCA vascular territory after cardiac operation (p = 0.035 for interaction). Perfusion changes were most notable in distal territories of the MCA and posterior communicating artery at 6 weeks, with no additional changes at 1 year. Postoperative increases in MCA perfusion at 6 weeks were associated with improved psychomotor speed (ß = 0.35, p = 0.016), whereas no important differences were found between the groups in vascular territory perfusion and cognition at 1 year. CONCLUSIONS: Cardiac operation is associated with important short-term increases in MCA perfusion with associated improvements in psychomotor speed.

Resting-State Functional Connectivity and Cognition After Major Cardiac Surgery in Older Adults without Preoperative Cognitive Impairment: Preliminary Findings.

OBJECTIVES: To look for changes in intrinsic functional brain connectivity associated with postoperative changes in cognition, a common complication in seniors undergoing major surgery, using resting-state functional magnetic resonance imaging. DESIGN: Objective cognitive testing and functional brain imaging were prospectively performed at preoperative baseline and 6 weeks after surgery and at the same time intervals in nonsurgical controls. SETTING: Academic medical center. PARTICIPANTS: Older adults undergoing cardiac surgery (n = 12) and nonsurgical older adult controls with a history of coronary artery disease (n = 12); no participants had cognitive impairment at preoperative baseline (Mini-Mental State Examination score >27). MEASUREMENTS: Differences in resting-state functional connectivity (RSFC) and global cognitive change relationships were assessed using a voxel-wise intrinsic connectivity method, controlling for demographic factors and pre- and perioperative cerebral white matter disease volume. Analyses were corrected for multiple comparisons (false discovery rate P < .01). RESULTS: Global cognitive change after cardiac surgery was significantly associated with intrinsic RSFC changes in regions of the posterior cingulate cortex and right superior frontal gyrus-anatomical and functional locations of the brain's default mode network (DMN). No statistically significant relationships were found between global cognitive change and RSFC change in nonsurgical controls. CONCLUSION: Clinicians have long known that some older adults develop postoperative cognitive dysfunction (POCD) after anesthesia and surgery, yet the neurobiological correlates of POCD are not well defined. The current results suggest that altered RSFC in specific DMN regions is positively correlated with global cognitive change 6 weeks after cardiac surgery, suggesting that DMN activity and connectivity could be important diagnostic markers of POCD or intervention targets for potential POCD treatment efforts.

Differentiating sensitivity of post-stimulus undershoot under diffusion weighting: implication of vascular and neuronal hierarchy.

The widely used blood oxygenation level dependent (BOLD) signal during brain activation, as measured in typical fMRI methods, is composed of several distinct phases, the last of which, and perhaps the least understood, is the post-stimulus undershoot. Although this undershoot has been consistently observed, its hemodynamic and metabolic sources are still under debate, as evidences for sustained blood volume increases and metabolic activities have been presented. In order to help differentiate the origins of the undershoot from vascular and neuronal perspectives, we applied progressing diffusion weighting gradients to investigate the BOLD signals during visual stimulation. Three distinct regions were established and found to have fundamentally different properties in post-stimulus signal undershoot. The first region, with a small but focal spatial extent, shows a clear undershoot with decreasing magnitude under increasing diffusion weighting, which is inferred to represent intravascular signal from larger vessels with large apparent diffusion coefficients (ADC), or high mobility. The second region, with a large continuous spatial extent in which some surrounds the first region while some spreads beyond, also shows a clear undershoot but no change in undershoot amplitude with progressing diffusion weighting. This would indicate a source based on extravascular and small vessel signal with smaller ADC, or lower mobility. The third region shows no significant undershoot, and is largely confined to higher order visual areas. Given their intermediate ADC, it would likely include both large and small vessels. Thus the consistent observation of this third region would argue against a vascular origin but support a metabolic basis for the post-stimulus undershoot, and would appear to indicate a lack of sustained metabolic rate likely due to a lower oxygen metabolism in these higher visual areas. Our results are the first, to our knowledge, to suggest that the post-stimulus undershoots have a spatial dependence on the vascular and neuronal hierarchy, and that progressing flow-sensitized diffusion weighting can help delineate these dependences.

Endogenous functional CBV contrast revealed by diffusion weighting.

Functional MRI (fMRI) based on the blood oxygenation level dependent (BOLD) contrast often suffers from a lack of specificity because of the vascular spread of oxygenation changes. It is suggested from the optical imaging and animal fMRI literature that cerebral blood volume (CBV) changes are more closely tied to the smaller vessels. As such, fMRI contrast based on CBV changes will have improved spatial specificity to the neuronal activities as they are immediately adjacent to the smaller vessels. In this paper, an endogenous contrast mechanism based on a diffusion weighting strategy that could detect functional CBV changes is presented. Initially, a theoretical framework is presented to model the functional signal changes as a function of CBV under diffusion weighting, which predicts peak CBV sensitivity at various vessel-tissue mixtures. It was found that a b factor over 1500 s/mm(2) would be necessary to achieve dominant CBV contrast. Further, two sets of experimental results are also presented. In the first experiment, diffusion weighting at a set of b factors ranging from 300 to 600 s/mm(2) was used. The results indicated that while the positive activation (predominantly BOLD signal) continued to reduce in magnitude and spatial extent, the negative activation (predominantly CBV signal) remained virtually constant with increasing b factors. The second experiment used a b factor of 1600 s/mm(2) and showed extensive negative activation in the visual cortex and greatly reduced positive activations compared with images with no diffusion weighting. The time course of negative activation showed a faster time to peak and return to baseline than the positive BOLD activity, consistent with the small vessel origin of the signal changes. These results suggest that appropriate diffusion weighting could be used to measure activation related CBV changes.

B factor dependence of the temporal characteristics of brain activation using dynamic apparent diffusion coefficient contrast.

Functional MRI studies to date have been generally performed using the blood oxygenation level dependent (BOLD) contrast mechanism. Recently, it has been proposed that dynamic change in the apparent diffusion coefficient (ADC), measured using intravoxel incoherent motion (IVIM) weighting, can be used as a robust functional contrast mechanism. Based on the differences in the timing characteristics compared to the BOLD activation, the ADC contrast can be selectively sensitized to upstream vascular pools (e.g., arterial networks). In this study we further investigated the timing characteristics of the functional ADC contrast using multiple degrees of IVIM weighting. It was found that the time course in the high b factor range lagged behind that of the low b factor range, indicating that the low b factor ADC contrast included contributions from the larger and faster moving arteries, and the smaller arterioles and capillaries downstream were reflected in the high b factor changes. These changes help confirm the arterial origin of the ADC contrast and offer a direction to improve the localization of activity to small vessel networks.