Faculty Bibliography

In a longitudinal study of recovery of left neglect following stroke using reaction time computerized assessment, we find that lateralized spatial deficits of attention and perception to be more severe than disturbance of action. Perceptual-attention deficits also show the most variability in the course of recovery, making them prime candidates for intervention. In an anatomical analysis of MRI findings, ventral frontal cortex damage was correlated with the most severe neglect, reflecting impaired fronto-parietal communication.

Scale-free dynamics, with a power spectrum following P proportional to f(-beta), are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with beta being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications.

As functional magnetic resonance imaging (fMRI) has become a driving force in cognitive neuroscience, it is crucial to understand the neural basis of the fMRI signal. Here, we discuss a novel neurophysiological correlate of the fMRI signal, the slow cortical potential (SCP), which also seems to modulate the power of higher-frequency activity, the more established neurophysiological correlate of the fMRI signal. We further propose a hypothesis for the involvement of the SCP in the emergence of consciousness, and review existing data that lend support to our proposal. This hypothesis, unlike several previous theories of consciousness, is firmly rooted in physiology and as such is entirely amenable to empirical testing.

Spontaneous fluctuations in the blood-oxygen-level-dependent (BOLD) signals demonstrate consistent temporal correlations within large-scale brain networks associated with different functions. The neurophysiological correlates of this phenomenon remain elusive. Here, we show in humans that the slow cortical potentials recorded by electrocorticography demonstrate a correlation structure similar to that of spontaneous BOLD fluctuations across wakefulness, slow-wave sleep, and rapid-eye-movement sleep. Gamma frequency power also showed a similar correlation structure but only during wakefulness and rapid-eye-movement sleep. Our results provide an important bridge between the large-scale brain networks readily revealed by spontaneous BOLD signals and their underlying neurophysiology.

Slow (<0.1 Hz), spontaneous fluctuations in the functional magnetic resonance imaging blood oxygen level-dependent (BOLD) signal have been shown to exhibit phase coherence within functionally related areas of the brain. Surprisingly, this phenomenon appears to transcend levels of consciousness. The genesis of coherent BOLD fluctuations remains to be fully explained. We present a resting state functional connectivity study of a 6-year-old child with a radiologically normal brain imaged both before and after complete section of the corpus callosum for the treatment of intractable epilepsy. Postoperatively, there was a striking loss of interhemispheric BOLD correlations with preserved intrahemispheric correlations. These unique data provide important insights into the relationship between connectional anatomy and functional organization of the human brain. Such observations have the potential to increase our understanding of large-scale brain systems in health and disease as well as improve the treatment of neurologic disorders.

PURPOSE OF REVIEW: Basic and translational neuroscience findings indicate that normal brain function depends on activity synchronization within distributed brain networks. This conclusion suggests a view of how brain injury causes behavioral deficits that differs from traditional localizationist views. RECENT FINDINGS: Novel functional neuroimaging methods demonstrate coherent activity in large-scale networks not only during task performance but also, surprisingly, at rest (i.e. in the absence of stimuli, tasks, or overt responses). Furthermore, breakdown of activity coherence at rest, even in regions of the brain that are structurally intact, correlates with behavioral deficits and their recovery after injury. Breakdown of functional connectivity appears to occur not just after local injury but also in other conditions that affect large-scale neural communication. SUMMARY: A network perspective is fundamental to appreciating the pathophysiology of brain injury at the systems level and the underlying mechanisms of recovery, and for developing novel strategies of rehabilitation.

Unilateral spatial neglect (neglect) is a syndrome characterized by perceptual deficits that prevent patients from attending and responding to the side of space and of the body opposite a damaged hemisphere (contralesional side). Neglect also involves motor deficits: patients may be slower to initiate a motor response to targets appearing in the left hemispace, even when using their unaffected arm (directional hypokinesia). Although this impairment is well known, its anatomical correlate has not been established. We tested 52 patients with neglect after right hemisphere stroke, and conducted an anatomical analysis on 29 of them to find the anatomical correlate of directional hypokinesia. We found that patients with directional hypokinesia had a lesion involving the ventral lateral putamen, the claustrum, and the white matter underneath the frontal lobe. Most importantly, none of the patients without directional hypokinesia had a lesion in the same region. The localization of neglect's motor deficits to the basal ganglia establishes interesting homologies with animal data; it also suggests that a relative depletion of dopamine in the nigrostriatal pathway on the same side of the lesion may be an important pathophysiological mechanism potentially amenable to intervention.

Spatial neglect is a syndrome following stroke manifesting attentional deficits in perceiving and responding to stimuli in the contralesional field. We examined brain network integrity in patients with neglect by measuring coherent fluctuations of fMRI signals (functional connectivity). Connectivity in two largely separate attention networks located in dorsal and ventral frontoparietal areas was assessed at both acute and chronic stages of recovery. Connectivity in the ventral network, part of which directly lesioned, was diffusely disrupted and showed no recovery. In the structurally intact dorsal network, interhemispheric connectivity in posterior parietal cortex was acutely disrupted but fully recovered. This acute disruption, and disrupted connectivity in specific pathways in the ventral network, strongly correlated with impaired attentional processing across subjects. Lastly, disconnection of the white matter tracts connecting frontal and parietal cortices was associated with more severe neglect and more disrupted functional connectivity. These findings support a network view in understanding neglect.