Sharp wave ripples (SPW-Rs) represent the most synchronous population pattern in the mammalian brain. Their excitatory output affects a wide area of the cortex and several subcortical nuclei. SPW-Rs occur during "off-line" states of the brain, associated with consummatory behaviors and non-REM sleep, and are influenced by numerous neurotransmitters and neuromodulators. They arise from the excitatory recurrent system of the CA3 region and the SPW-induced excitation brings about a fast network oscillation (ripple) in CA1. The spike content of SPW-Rs is temporally and spatially coordinated by a consortium of interneurons to replay fragments of waking neuronal sequences in a compressed format. SPW-Rs assist in transferring this compressed hippocampal representation to distributed circuits to support memory consolidation; selective disruption of SPW-Rs interferes with memory. Recently acquired and pre-existing information are combined during SPW-R replay to influence decisions, plan actions and, potentially, allow for creative thoughts. In addition to the widely studied contribution to memory, SPW-Rs may also affect endocrine function via activation of hypothalamic circuits. Alteration of the physiological mechanisms supporting SPW-Rs leads to their pathological conversion, "p-ripples," which are a marker of epileptogenic tissue and can be observed in rodent models of schizophrenia and Alzheimer's Disease. Mechanisms for SPW-R genesis and function are discussed in this review.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/hipo.22488

Hippocampal sharp wave‐ripple: A cognitive biomarker for episodic memory and planning

Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we developed new devices that integrate ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors that are connected using fewer wires. We used this system to record spatial properties of cat brain activity in vivo, including sleep spindles, single-trial visual evoked responses and electrographic seizures. We found that seizures may manifest as recurrent spiral waves that propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface devices.

/pdf/flexible-foldable-actively-multiplexed-high-density-2y9l2n62qa.pdf

Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo

Advances in materials, mechanics, and manufacturing now allow construction of high-quality electronics and optoelectronics in forms that can readily integrate with the soft, curvilinear, and time-dynamic surfaces of the human body. The resulting capabilities create new opportunities for studying disease states, improving surgical procedures, monitoring health/wellness, establishing human-machine interfaces, and performing other functions. This review summarizes these technologies and illustrates their use in forms integrated with the brain, the heart, and the skin.

https://www.annualreviews.org/doi/pdf/10.1146/annurev-bioeng-071811-150018

Flexible and Stretchable Electronics for Biointegrated Devices

Seizures can occur spontaneously and in a recurrent manner, which defines epilepsy; or they can be induced in a normal brain under a variety of conditions in most neuronal networks and species from flies to humans. Such universality raises the possibility that invariant properties exist that characterize seizures under different physiological and pathological conditions. Here, we analysed seizure dynamics mathematically and established a taxonomy of seizures based on first principles. For the predominant seizure class we developed a generic model called Epileptor. As an experimental model system, we used ictal-like discharges induced in vitro in mouse hippocampi. We show that only five state variables linked by integral-differential equations are sufficient to describe the onset, time course and offset of ictal-like discharges as well as their recurrence. Two state variables are responsible for generating rapid discharges (fast time scale), two for spike and wave events (intermediate time scale) and one for the control of time course, including the alternation between ‘normal’ and ictal periods (slow time scale). We propose that normal and ictal activities coexist: a separatrix acts as a barrier (or seizure threshold) between these states. Seizure onset is reached upon the collision of normal brain trajectories with the separatrix. We show theoretically and experimentally how a system can be pushed toward seizure under a wide variety of conditions. Within our experimental model, the onset and offset of ictal-like discharges are well-defined mathematical events: a saddle-node and homoclinic bifurcation, respectively. These bifurcations necessitate a baseline shift at onset and a logarithmic scaling of interspike intervals at offset. These predictions were not only confirmed in our in vitro experiments, but also for focal seizures recorded in different syndromes, brain regions and species (humans and zebrafish). Finally, we identified several possible biophysical parameters contributing to the five state variables in our model system. We show that these parameters apply to specific experimental conditions and propose that there exists a wide array of possible biophysical mechanisms for seizure genesis, while preserving central invariant properties. Epileptor and the seizure taxonomy will guide future modeling and translational research by identifying universal rules governing the initiation and termination of seizures and predicting the conditions necessary for those transitions.

/pdf/on-the-nature-of-seizure-dynamics-4cxq3m9jxu.pdf

On the nature of seizure dynamics

SUMMARY High-frequency oscillations (HFOs) in the 80– 200 Hz range can be recorded from normal hippocampus and parahippocampal structures of humans and animals. They are believed to reflect inhibitory field potentials, which facilitate information transfer by synchronizing neuronal activity over long distances. HFOs in the range of 250– 600 Hz (fast ripples, FRs) are pathologic and are readily recorded from hippocampus and parahippocampal structures of patients with mesial temporal lobe epilepsy, as well as rodent models of this disorder. These oscillations, and similar HFOs recorded from neocortex of patients, appear to identify brain tissue capable of spontaneous ictogenesis and are believed to reflect the neuronal substrates of epileptogenesis and epileptogenicity. The distinction between normal and pathologic HFOs (pHFOs), however, cannot be made on the basis of frequency alone, as oscillations in the FR frequency range can be recorded from some areas of normal neocortex, whereas oscillations in the ripple frequency range are present in epileptic dentate gyrus where normal ripples never occur and, therefore, appear to be pathologic. The suggestion that FRs may be harmonics of normal ripples is unlikely, because of their spatially distinct generators, and evidence that FRs reflect synchronized firing of abnormally bursting neurons rather than inhibitory field potentials. These synchronous population spikes, however, can fire at ripple frequencies, and their harmonics appear to give rise to FRs. Investigations into the fundamental neuronal processes responsible for pHFOs could provide insights into basic mechanisms of epilepsy. The potential for pHFOs to act as biomarkers for epileptogenesis and epileptogenicity is also discussed.

/pdf/high-frequency-oscillations-what-is-normal-and-what-is-not-4h9gkw2qj9.pdf

High-frequency oscillations : What is normal and what is not?

Neuronal oscillations span a wide range of spatial and temporal scales that extend beyond traditional clinical EEG. Recent research suggests that high-frequency oscillations (HFO), in the ripple (80-250 Hz) and fast ripple (250-1000 Hz) frequency range, may be signatures of epileptogenic brain and involved in the generation of seizures. However, most research investigating HFO in humans comes from microwire recordings, whose relationship to standard clinical intracranial EEG (iEEG) has not been explored. In this study iEEG recordings (DC - 9000 Hz) were obtained from human medial temporal lobe using custom depth electrodes containing both microwires and clinical macroelectrodes. Ripple and fast-ripple HFO recorded from both microwires and clinical macroelectrodes were increased in seizure generating brain regions compared to control regions. The distribution of HFO frequencies recorded from the macroelectrodes was concentrated in the ripple frequency range, compared to a broad distribution of HFO frequencies recorded from microwires. The average frequency of ripple HFO recorded from macroelectrodes was lower than that recorded from microwires (143.3 +/- 49.3 Hz versus 116.3 +/- 38.4, Wilcoxon rank sum P<0.0001). Fast-ripple HFO were most often recorded on a single microwire, supporting the hypothesis that fast-ripple HFO are primarily generated by highly localized, sub-millimeter scale neuronal assemblies that are most effectively sampled by microwire electrodes. Future research will address the clinical utility of these recordings for localizing epileptogenic networks and understanding seizure generation.

/pdf/high-frequency-oscillations-in-human-temporal-lobe-1xun9l7b2u.pdf

High-frequency oscillations in human temporal lobe : simultaneous microwire and clinical macroelectrode recordings

Multiple mechanisms of 5-flourouracil (5-fu)-associated chest pain in a patient with metastatic sigmoid cancer


 Mrs. Z is a 56-year-old woman with a long history of symptomatic paroxysmal supraventricular tachycardia (PSVT) who presented with neck and back pain. MRI of cervical and thoracic spine revealed an abnormal signal in the right mediastinal area. A chest CT demonstrated a lobulated 5.8 x 5.5 x 3.5 cm, fluid density lesion contiguous with the pericardium adjacent to right atrium (RA) and inferior venacava (IVC) without wall thickening or solid components, consistent with a pericardial cyst (PC). A transthoracic echo (Panel B) revealed normal left ventricular size and systolic function with an EF of 66%. An echolucency adjacent to the RA and IVC consistent with a pericardial cyst was noted without any extrinsic compression. Given her asymptomatic presentation and normal cardiac imaging, a shared decision was made to conservatively manage.Two years ago, she underwent ablation for AVNRT, followed by an ablation for atrial tachycardia (AT). She continues to have short, symptomatic runs of AT (
 Panel A
 ). A recent CMR re-demonstrated a large, septated pericardial cyst (6.2 x 5 cm) abutting the RA and IVC (
 Panel C
 ). Given her on-going symptomatic SVT, she is referred for robotically assisted thoracoscopic surgery despite stability in size.
 
 
 Discussion:
 PCs are rare but typically benign. They are the third most common and account for 6% of mediastinal masses. They can be congenital or acquired, simple or complex, and have a predilection for R costophrenic angle (50-70%) followed by the L costophrenic angle (28-38%). Although most are asymptomatic and diagnosed incidentally, they sometimes can result in symptoms such as chest pain, dyspnea, and paroxysmal tachyarrhythmias. Large PCs can lead to tamponade. If a PC is suspected by CXR or echo, cardiac CT or CMR are used for confirmation. Periodic imaging is recommended every 1-2 yr. Most PCs resolve spontaneously. Treatment options include aspiration or surgical resection. Minimally invasive surgical options appear to be the best.
 
 
 


Gregory J. Cascino

Papers

High-frequency oscillations in human temporal lobe : simultaneous microwire and clinical macroelectrode recordings

Multiple mechanisms of 5-flourouracil (5-fu)-associated chest pain in a patient with metastatic sigmoid cancer

Abstract 14217: Needs Must: A Not-So Benign Pericardial Cyst