Faculty Bibliography

Voltage-sensitive dye imaging of mouse thalamocortical slices demonstrated that electrical stimulation of the centrolateral intralaminar thalamic nucleus (CL) resulted in the specific activation of thalamic reticular nucleus, striatum/putamen, and cortical layers 5, 6, and 1. By contrast, ventrobasal (VB) thalamic stimulation, while activating the reticular and basal ganglia nuclei, also activated directly layers 4 and deep 5 of the cortex. Conjoined stimulation of the VB and CL nuclei resulted in supralinear summation of the two inputs at cortical output layer 5, demonstrating coincidence detection along the apical dendrites. This supralinear summation was also noticed at gamma band stimulus frequency ( approximately 40 Hz). Direct stimulation of cortical layer 1, after a radial section of the cortex that spared only that layer, was shown to sum supralinearly with the cortical activation triggered by VB stimulation, providing a second demonstration for coincidence detection. Coincidence detection by coactivation of the specific (VB) and nonspecific (CL) thalamic nuclei has been proposed as the basis for the temporal conjunction that supports cognitive binding in the brain

Spatiotemporal profiles of ensemble subthreshold neuronal oscillation were studied in brainstem slices using high-speed voltage-sensitive dye imaging. After local electrical stimuli, the overall voltage profile demonstrated coherent oscillatory waves that spread over the inferior olive (IO). These oscillations were also observed in concurrently obtained intracellular recordings from IO neurons. Over the first few seconds after the stimuli, the optically recorded oscillations clustered into coherent groups comprising hundreds of neurons. Statistical analysis of the spatial profiles of these clusters revealed size fluctuation around stable core regions that were surrounded by a rim the diameter of which varied in time during the oscillation period. The neuronal ensemble oscillations were calcium derived and had an average frequency range of 1-7 Hz. This rhythmic response demonstrated a different spatiotemporal distribution in the presence of picrotoxin, which induced the merging of neuronal clusters into larger areas of coherent activity. The possibility that such clustering is a consequence of intrinsic oscillations in ensembles of coupled neurons was tested using mathematical modeling

Evoked magnetic fields were recorded while human subjects perceived apparent motion (AM) or 2 static bars of light separated by 1deg. Flash duration was 1ms and stimulus onset asynchrony (SOA) was 0 or 40ms. There were 3 tasks: left, right, or no AM. Detailed psychometric curves of the min SOA of AM were obtained separately. AM was perceived with a probability of .5 and 1 for SOAs of 15 and 40ms, respectively. Signals were processed with ICA for artifact removal, and then averaged. Amplitude and phase information in the time-frequency domain were estimated by the gabor wavelet transform. The mean sensor power revealed a stimulus-locked burst of gamma, beta and 10Hz activity. The AM conditions had enhanced and more long-lasting gamma power. Sparse source estimates were computed with an anatomically constrained recursively weighted minimum-norm algorithm modified to minimize the total current density. The source space was constrained to the subsampled cortical surfaces and to sparse subcortical dipoles. Source estimates were computed for each time point, each independent component, and for time-frequency subspaces of the wavelet transformed signals. Enhanced dynamic patterns in cortical areas V1, V3A, hMT+, LG, FG, LOS, IPS, STS, and other clusters in parietal, frontal, and temporal lobe, and in LGN, pulvinar, and superior colliculi correlated with AM. Dynamic gamma band sources were reconstructed in many of the motion-sensitive visual areas, particularly in V3A, hMT+, parietal and temporal cortex. Our results support a role for quantal gamma band and recurrent network activity in the creation of AM qualia by integrating bottom-up and top-down processes

This report identifies evidence of partially functional cerebral regions in catastrophically injured brains. To study five patients in a persistent vegetative state (PVS) with different behavioural features, we employed [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET), MRI and magnetoencephalographic (MEG) responses to sensory stimulation. Each patient's brain expressed a unique metabolic pattern. In three of the five patients, co-registered PET/MRI correlate islands of relatively preserved brain metabolism with isolated fragments of behaviour. Two patients had suffered anoxic injuries and demonstrated marked decreases in overall cerebral metabolism to 30-40% of normal. Two other patients with non-anoxic, multifocal brain injuries demonstrated several isolated brain regions with relatively higher metabolic rates, that ranged up to 50-80% of normal. Nevertheless, their global metabolic rates remained <50% of normal. MEG recordings from three PVS patients provide clear evidence for the absence, abnormality or reduction of evoked responses. Despite major abnormalities, however, these data also provide evidence for localized residual activity at the cortical level. Each patient partially preserved restricted sensory representations, as evidenced by slow evoked magnetic fields and gamma band activity. In two patients, these activations correlate with isolated behavioural patterns and metabolic activity. Remaining active regions identified in the three PVS patients with behavioural fragments appear to consist of segregated corticothalamic networks that retain connectivity and partial functional integrity. A single patient who suffered severe injury to the tegmental mesencephalon and paramedian thalamus showed widely preserved cortical metabolism, and a global average metabolic rate of 65% of normal. The relatively high preservation of cortical metabolism in this patient defines the first functional correlate of clinical- pathological reports associating permanent unconsciousness with structural damage to these regions. The specific patterns of preserved metabolic activity identified in these patients do not appear to represent random survivals of a few neuronal islands; rather they reflect novel evidence of the modular nature of individual functional networks that underlie conscious brain function. The variations in cerebral metabolism in chronic PVS patients indicate that some cerebral regions can retain partial function in catastrophically injured brains

OBJECTIVE: To minimize the risks associated with treating cortical cerebral arteriovenous malformations (AVMs), we developed a technique combining functional imaging and cerebral angiography. The functional loci obtained by performing magnetoencephalography (MEG) are projected onto stereoscopic pairs of a stereotactically derived digital subtraction angiogram. The result is a simultaneous three-dimensional perspective of the angioarchitecture of an AVM and its relationship to the sensorimotor cortex. METHODS: Eight patients underwent multimodality brain imaging, including magnetic resonance imaging, functional mapping via MEG, and stereotactic angiography using a modified Compass fiducial system (Compass International, Rochester, MN). The coordinates derived by performing MEG were superimposed onto stereotactic, stereoscopic, angiographic pairs using custom-made distortion correction and coordinate transfer software. RESULTS: The magnetoencephalographic angiogram allowed simultaneous viewing of the angioarchitecture of the AVM nidus, the feeding vessels, and the draining veins and their relationship to the normal cerebral vasculature and functional cortex. This imaging technique was particularly valuable in identifying en passant vessels that supplied functional cortex and was used during the treatment of these lesions. CONCLUSION: The techniques of MEG and cerebral angiography were combined to provide simultaneous viewing of both modalities in a three-dimensional perspective. This technique can aid in risk stratification in the management of patients with cerebral AVMs. In addition, this technique can facilitate the selective targeting of vessels, thus potentially reducing the risks associated with embolization of these formidable lesions

Thalamocortical dysrhythmias (TCD) may underlie a variety of neurological and neuropsychiatric symptoms. (1,2) In TCD, pathological theta-range activity from thalamic deafferentation or disfacilitation is hypothesized to trigger thalamocortical (TC) domains to oscillate at low frequency, underlying negative symptoms, surrounded by areas of gamma-band activity, creating an 'edge effect' leading to some positive symptoms. TC connectivity and neuronal properties can distribute and sustain this pathological equilibrium. Spontaneous neuromagnetic activity was recorded from patients (n=5) with refractory OCD and from controls (n=4). Recordings were performed with whole-head MEG (4D Neuroimaging), for 5-10 min (0.1-508Hz) with subjects' eyes closed. Coherence, multitaper-based spectral and independent component analyses (ICA) were performed using Matlab (Mathworks) and in-house software. Power spectra from control recordings demonstrated typical alpha rhythms, while spectra from OCD subjects showed robust activity in the theta range and increased total power. In addition, cross-correlations of spectral amplitude from controls displayed activation of discrete frequencies; patterns from OCD subjects showed high coherence over a wider spectral range. Furthermore, ICA revealed components with theta-range spectral properties and dipolar positions consistent with aberrant resting cortical and basal ganglia oscillations. The conception of TCD may serve as a template for the study and treatment of neurological and psychiatric disorders. 1.Llinas,R et al (1999) PNAS 96:15222-7 2.Llinas,R et al (2001) Thal Rel Sys 1:237-44