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Enhanced Interplay of Neuronal Coherence and Coupling in the Dying Human Brain
Vicente, Raul; Rizzuto, Michael; Sarica, Can; Yamamoto, Kazuaki; Sadr, Mohammed; Khajuria, Tarun; Fatehi, Mostafa; Moien-Afshari, Farzad; Haw, Charles S; Llinas, Rodolfo R; Lozano, Andres M; Neimat, Joseph S; Zemmar, Ajmal
The neurophysiological footprint of brain activity after cardiac arrest and during near-death experience (NDE) is not well understood. Although a hypoactive state of brain activity has been assumed, experimental animal studies have shown increased activity after cardiac arrest, particularly in the gamma-band, resulting from hypercapnia prior to and cessation of cerebral blood flow after cardiac arrest. No study has yet investigated this matter in humans. Here, we present continuous electroencephalography (EEG) recording from a dying human brain, obtained from an 87-year-old patient undergoing cardiac arrest after traumatic subdural hematoma. An increase of absolute power in gamma activity in the narrow and broad bands and a decrease in theta power is seen after suppression of bilateral hemispheric responses. After cardiac arrest, delta, beta, alpha and gamma power were decreased but a higher percentage of relative gamma power was observed when compared to the interictal interval. Cross-frequency coupling revealed modulation of left-hemispheric gamma activity by alpha and theta rhythms across all windows, even after cessation of cerebral blood flow. The strongest coupling is observed for narrow- and broad-band gamma activity by the alpha waves during left-sided suppression and after cardiac arrest. Albeit the influence of neuronal injury and swelling, our data provide the first evidence from the dying human brain in a non-experimental, real-life acute care clinical setting and advocate that the human brain may possess the capability to generate coordinated activity during the near-death period.
PMCID:8902637
PMID: 35273490
ISSN: 1663-4365
CID: 5190852
Broadening the definition of a nervous system to better understand the evolution of plants and animals
Miguel-Tomé, Sergio; Llinás, Rodolfo R
Most textbook definitions recognize only animals as having nervous systems. However, for the past couple decades, botanists have been meticulously studying long-distance signaling systems in plants, and some researchers have stated that plants have a simple nervous system. Thus, an academic conflict has emerged between those who defend and those who deny the existence of a nervous system in plants. This article analyses that debate, and we propose an alternative to answering yes or no: broadening the definition of a nervous system to include plants. We claim that a definition broader than the current one, which is based only on a phylogenetic viewpoint, would be helpful in obtaining a deeper understanding of how evolution has driven the features of signal generation, transmission and processing in multicellular beings. Also, we propose two possible definitions and exemplify how broader a definition allows for new viewpoints on the evolution of plants, animals and the nervous system.
PMID: 34120565
ISSN: 1559-2324
CID: 4916412
Poststroke acute dysexecutive syndrome, a disorder resulting from minor stroke due to disruption of network dynamics
Marsh, Elisabeth B; Brodbeck, Christian; Llinas, Rafael H; Mallick, Dania; Kulasingham, Joshua P; Simon, Jonathan Z; Llinás, Rodolfo R
Stroke patients with small central nervous system infarcts often demonstrate an acute dysexecutive syndrome characterized by difficulty with attention, concentration, and processing speed, independent of lesion size or location. We use magnetoencephalography (MEG) to show that disruption of network dynamics may be responsible. Nine patients with recent minor strokes and eight age-similar controls underwent cognitive screening using the Montreal cognitive assessment (MoCA) and MEG to evaluate differences in cerebral activation patterns. During MEG, subjects participated in a visual picture-word matching task. Task complexity was increased as testing progressed. Cluster-based permutation tests determined differences in activation patterns within the visual cortex, fusiform gyrus, and lateral temporal lobe. At visit 1, MoCA scores were significantly lower for patients than controls (median [interquartile range] = 26.0 [4] versus 29.5 [3], P = 0.005), and patient reaction times were increased. The amplitude of activation was significantly lower after infarct and demonstrated a pattern of temporal dispersion independent of stroke location. Differences were prominent in the fusiform gyrus and lateral temporal lobe. The pattern suggests that distributed network dysfunction may be responsible. Additionally, controls were able to modulate their cerebral activity based on task difficulty. In contrast, stroke patients exhibited the same low-amplitude response to all stimuli. Group differences remained, to a lesser degree, 6 mo later; while MoCA scores and reaction times improved for patients. This study suggests that function is a globally distributed property beyond area-specific functionality and illustrates the need for longer-term follow-up studies to determine whether abnormal activation patterns ultimately resolve or another mechanism underlies continued recovery.
PMID: 33318200
ISSN: 1091-6490
CID: 4717672
Noninvasive muscle activity imaging using magnetography
Llinás, Rodolfo R; Ustinin, Mikhail; Rykunov, Stanislav; Walton, Kerry D; Rabello, Guilherme M; Garcia, John; Boyko, Anna; Sychev, Vyacheslav
A spectroscopic paradigm has been developed that allows the magnetic field emissions generated by the electrical activity in the human body to be imaged in real time. The growing significance of imaging modalities in biology is evident by the almost exponential increase of their use in research, from the molecular to the ecological level. The method of analysis described here allows totally noninvasive imaging of muscular activity (heart, somatic musculature). Such imaging can be obtained without additional methodological steps such as the use of contrast media.
PMID: 32071237
ISSN: 1091-6490
CID: 4312222
Space and time in the brain
Buzsaki, Gyorgy; Llinas, Rodolfo
Nothing is more intuitive, yet more complex, than the concepts of space and time. In contrast to spacetime in physics, space and time in neuroscience remain separate coordinates to which we attach our observations. Investigators of navigation and memory relate neuronal activity to position, distance, time point, and duration and compare these parameters to units of measuring instruments. Although spatial-temporal sequences of brain activity often correlate with distance and duration measures, these correlations may not correspond to neuronal representations of space or time. Neither instruments nor brains sense space or time. Neuronal activity can be described as a succession of events without resorting to the concepts of space or time. Instead of searching for brain representations of our preconceived ideas, we suggest investigating how brain mechanisms give rise to inferential, model-building explanations.
PMCID:5998813
PMID: 29074768
ISSN: 1095-9203
CID: 3011962
Perspective on calcium and Alzheimer's disease [Letter]
Llinas, Rodolfo; Moreno, Herman
PMID: 28130964
ISSN: 1552-5279
CID: 2459622
Differential Modulation of Rhythmic Brain Activity in Healthy Adults by a T-Type Calcium Channel Blocker: An MEG Study
Walton, Kerry D; Maillet, Emeline L; Garcia, John; Cardozo, Timothy; Galatzer-Levy, Isaac; Llinas, Rodolfo R
1-octanol is a therapeutic candidate for disorders involving the abnormal activation of the T-type calcium current since it blocks this current specifically. Such disorders include essential tremor and a group of neurological and psychiatric disorders resulting from thalamocortical dysrhythmia (TCD). For example, clinically, the observable phenotype in essential tremor is the tremor itself. The differential diagnostic of TCD is not based only on clinical signs and symptoms. Rather, TCD incorporates an electromagnetic biomarker, the presence of abnormal thalamocortical low frequency brain oscillations. The effect of 1-octanol on brain activity has not been tested. As a preliminary step to such a TCD study, we examined the short-term effects of a single dose of 1-octanol on resting brain activity in 32 healthy adults using magnetoencephalograpy. Visual inspection of baseline power spectra revealed that the subjects fell into those with strong low frequency activity (set 2, n = 11) and those without such activity, but dominated by an alpha peak (set 1, n = 22). Cross-validated linear discriminant analysis, using mean spectral density (MSD) in nine frequency bands as predictors, found overall that 82.5% of the subjects were classified as determined by visual inspection. The effect of 1-octanol on the MSD in narrow frequency bands differed between the two subject groups. In set 1 subjects the MSD increased in the 4.5-6.5Hz and 6.5-8.5 Hz bands. This was consistent with a widening of the alpha peak toward lower frequencies. In the set two subjects the MSD decrease in the 2.5-4.5 Hz and 4.5-6.5 Hz bands. This decreased power is consistent with the blocking effect of 1-octanol on T-type calcium channels. The subjects reported no adverse effects of the 1-octanol. Since stronger low frequency activity is characteristic of patients with TCD, 1-octanol and other T-type calcium channel blockers are good candidates for treatment of this group of disorders following a placebo-controlled study.
PMCID:5289965
PMID: 28217089
ISSN: 1662-5161
CID: 2459782
Neuromuscular transmission and muscle fatigue changes by nanostructured oxygen
Ivannikov, Maxim V; Sugimori, Mutsuyuki; Llinas, Rodolfo R
INTRODUCTION: Oxygen (O2 ) nanobubbles offer a new method for tissue oxygenation. The effects of O2 nanobubbles on transmission at neuromuscular junctions (NMJs) and muscle function were explored in murine diaphragm. METHODS: Electrophysiological parameters, NMJ ultrastructure, muscle force, and muscle fatigue were studied during superfusion with solutions with different oxygen levels or oxygen nanobubbles. RESULTS: High frequency nerve stimulation of muscles superfused with O2 nanobubble solution slowed neurotransmission decline over those with either control or hyperoxic solution. O2 nanobubble solution increased the amplitude of evoked excitatory junction potentials and quantal content but did not affect spontaneous activity. Electron microscopy of stimulated O2 nanobubble treated NMJs showed accumulation of large synaptic vesicles and endosome-like structures. O2 nanobubble solution had no effects on isometric muscle force, but it significantly decreased fatigability and maximum force recovery time in nerve stimulated muscles. CONCLUSIONS: O2 nanobubbles increase neurotransmission and reduce the probability of neurotransmission failure in muscle fatigue
PMID: 27422738
ISSN: 1097-4598
CID: 2180312
[Software for the Partial Spectroscopy of Human Brain]
Rykunov, SD; Ustinin, MN; Polyanin, AG; Sychev, VV; Llinas, RR
ORIGINAL:0012212
ISSN: 1994-6538
CID: 2674212
Oscillation in the inferior olive neurons: Functional implication
Chapter by: Llinas, RR
in: Essentials of Cerebellum and Cerebellar Disorders: A Primer for Graduate Students by
pp. 293-298
ISBN: 9783319245515
CID: 2585112