Jason L. Gerrard

Sequence Reactivation in the Hippocampus Is Impaired in Aged Rats

The hippocampus is thought to coordinate memory consolidation by reactivating traces from behavioral experience when the brain is not actively processing new input. In fact, during slow-wave sleep, the patterns of CA1 pyramidal cell ensemble activity correlations are reactivated in both young and aged rats. In addition to correlated activity patterns, repetitive track running also creates a recurring sequence of pyramidal cell activity. The present study compared CA1 sequence activity pattern replay in young and old animals during rest periods after behavior. Whereas the young rats exhibited significant sequence reactivation, it was markedly impaired in the aged animals. When the spatial memory scores of all animals were compared with the degree of sequence reactivation, there was a significant correlation. The novel finding that weak replay of temporal patterns has behavioral consequences, strengthens the idea that reactivation processes are integral to memory consolidation.

Seizure control for intracranial arteriovenous malformations is directly related to treatment modality: a meta-analysis

Object Seizures are a common presenting sign of intracranial arteriovenous malformations (AVMs). The object of this meta-analysis was to determine if the modality selected to treat AVMs affects the rate of seizure outcomes. Methods All published data describing seizure status as an outcome goal over the past 20 years were included in this study. Seizure outcomes following microsurgery (MS), endovascular embolization for cure (EVE), or stereotactic radiosurgery (SRS) were compared using a validated random effect logistic regression approach. Results 24 studies, with a total of 1157 patients, were analyzed. Overall, the microsurgical group had the best seizure control (p<0.01), with the relative predicted rates of seizure outcome as follows: MS 78.3% (95% CI 70.1% to 85.8%); SRS 62.8% (95% CI 55.0% to 70.0%); and EVE 49.3% (95% CI 32.1% to 66.6%). Patients in the SRS group who had complete obliteration of their AVMs achieved the highest rate of seizure control (85.2% (95% CI 79.1% to 91.2%); p<0.01). The development of new onset seizures occurred more frequently in patients undergoing EVE (39.4% (95% CI 8.1% to 67.8%)) compared with MS (9.1% (95% CI 5.0% to 13.1%)) and SRS (5.4% (95% CI 3.0% to 7.8%)) (p<0.3 and p<0.01, respectively). Conclusions This is the first meta-analysis designed to study relative rates of seizure outcomes following the currently utilized AVM treatment modalities. In general, MS results in the highest proportion of seizure control. However, if SRS results in successful obliteration of the AVM, then this modality is the most effective in achieving seizure control.

The spatial and signal characteristics of physiologic high frequency oscillations

To study the incidence, spatial distribution, and signal characteristics of high frequency oscillations (HFOs) outside the epileptic network.

7T MR spectroscopic imaging in the localization of surgical epilepsy

With the success that surgical approaches can provide for localization‐related epilepsy, accurate seizure localization remains important. Although magnetic resonance (MR) spectroscopy has had success in earlier studies in medial temporal lobe epilepsy, there have been fewer studies evaluating its use in a broader range of localization‐related epilepsy. With improvements in signal‐to‐noise with ultra‐high field MR, we report on the use of high resolution 7T MR spectroscopic imaging (MRSI) in 25 surgically treated patients studied over a 3.5‐year period.

Gamma knife stereotactic radiosurgical thalamotomy for intractable tremor: A systematic review of the literature

Tremor markedly reduces quality of life and causes a significant psychological burden for patients who are severely affected by this movement disorder. Pharmacologic and surgical treatments for tremor exist, but for patients who have failed medical therapy and are not surgical candidates, stereotactic radiosurgery is the only available treatment option. Of available stereotactic radiosurgical techniques for intractable tremor, the authors chose to evaluate the safety and efficacy of gamma knife stereotactic radiosurgical thalamotomy. In order to qualitatively synthesize available data a systematic review was conducted by searching MEDLINE (OvidSP 1946-January Week 1 2014) and Embase (OvidSP 1974-2014 January). The search strategy was not limited by study design or language of publication. All searches were conducted on January 7, 2014. Treatment efficacy, adverse outcomes, and patient deaths were reviewed and tabulated. Complications appeared months to years post procedure and most commonly consisted of mild contralateral numbness and transient hemiparesis. Rarely, more severe complications were reported, including dysphagia and death. Though no data from randomized controlled trials are available, our analysis of the literature indicates that unilateral gamma knife thalamotomy using doses from 130 to 150Gy appears safe and well tolerated.

Reactivation of hippocampal ensemble activity patterns in the aging rat.

In young rats, the pattern of neuronal ensemble activity correlations expressed among hippocampal pyramidal cells during behavior persists during subsequent quiet wakefulness and slow-wave sleep, a process that may facilitate the consolidation of episodic memories. The present study explored the hypothesis that age-related changes in this process might contribute to memory impairments observed during normal aging. Neuronal activity was recorded from CA1 pyramidal cells, and in both young and old rats, there was a strong similarity between the resting epoch activity patterns and those from the preceding behavior epoch. This similarity was strongest during sharp-wave events. There were no detectable differences in the reactivation process or the decay rate between the young and old age groups. Thus, age differences in spatial memory do not appear to be explainable by differences in the spontaneous reactivation of familiar patterns within the hippocampus during the immediate postbehavior period.

Effect of age on burst firing characteristics of rat hippocampal pyramidal cells.

During behavior, hippocampal pyramidal cells emit high frequency bursts, modulated by the animals location and the 7 Hz theta rhythm. During rest, CA1 EEG exhibits large irregular activity (LIA), containing sharp-wave/ripple complexes, during which pyramidal cells exhibit burst discharge. Aging results in altered intracellular calcium homeostasis, increased electrical coupling and reduced cholinergic modulation within CA1, all of which might affect burst discharge characteristics. During LIA, old rats exhibited more short (3–7 ms) inter-spike intervals, with no change in mean firing rate. During behavior induced theta rhythm, however, interval distributions were not affected by age. Thus, different mechanisms must underlie burst discharge in theta and LIA states. Moreover, age related changes in the cholinergic system appear not to play a major role in shaping the temporal discharge characteristics of CA1 pyramidal cells. The mechanism and significance of the higher frequency bursting in old rats during LIA remains to be determined.

Restoring Conscious Arousal During Focal Limbic Seizures with Deep Brain Stimulation

Abstract Impaired consciousness occurs suddenly and unpredictably in people with epilepsy, markedly worsening quality of life and increasing risk of mortality. Focal seizures with impaired consciousness are the most common form of epilepsy and are refractory to all current medical and surgical therapies in about one‐sixth of cases. Restoring consciousness during and following seizures would be potentially transformative for these individuals. Here, we investigate deep brain stimulation to improve level of conscious arousal in a rat model of focal limbic seizures. We found that dual‐site stimulation of the central lateral nucleus of the intralaminar thalamus (CL) and the pontine nucleus oralis (PnO) bilaterally during focal limbic seizures restored normal‐appearing cortical electrophysiology and markedly improved behavioral arousal. In contrast, single‐site bilateral stimulation of CL or PnO alone was insufficient to achieve the same result. These findings support the “network inhibition hypothesis” that focal limbic seizures impair consciousness through widespread inhibition of subcortical arousal. Driving subcortical arousal function would be a novel therapeutic approach to some forms of refractory epilepsy and may be compatible with devices already in use for responsive neurostimulation. Multisite deep brain stimulation of subcortical arousal structures may benefit not only patients with epilepsy but also those with other disorders of consciousness.

Neurostimulation to improve level of consciousness in patients with epilepsy.

When drug-resistant epilepsy is poorly localized or surgical resection is contraindicated, current neurostimulation strategies such as deep brain stimulation and vagal nerve stimulation can palliate the frequency or severity of seizures. However, despite medical and neuromodulatory therapy, a significant proportion of patients continue to experience disabling seizures that impair awareness, causing disability and risking injury or sudden unexplained death. We propose a novel strategy in which neuromodulation is used not only to reduce seizures but also to ameliorate impaired consciousness when the patient is in the ictal and postictal states. Improving or preventing alterations in level of consciousness may have an effect on morbidity (e.g., accidents, drownings, falls), risk for death, and quality of life. Recent studies may have elucidated underlying networks and mechanisms of impaired consciousness and yield potential novel targets for neuromodulation. The feasibility, benefits, and pitfalls of potential deep brain stimulation targets are illustrated in human and animal studies involving minimally conscious/vegetative states, movement disorders, depth of anesthesia, sleep-wake regulation, and epilepsy. We review evidence that viable therapeutic targets for impaired consciousness associated with seizures may be provided by key nodes of the consciousness system in the brainstem reticular activating system, hypothalamus, basal ganglia, thalamus, and basal forebrain.

Hemifacial Spasm and Neurovascular Compression

Hemifacial spasm (HFS) is characterized by involuntary unilateral contractions of the muscles innervated by the ipsilateral facial nerve, usually starting around the eyes before progressing inferiorly to the cheek, mouth, and neck. Its prevalence is 9.8 per 100,000 persons with an average age of onset of 44 years. The accepted pathophysiology of HFS suggests that it is a disease process of the nerve root entry zone of the facial nerve. HFS can be divided into two types: primary and secondary. Primary HFS is triggered by vascular compression whereas secondary HFS comprises all other causes of facial nerve damage. Clinical examination and imaging modalities such as electromyography (EMG) and magnetic resonance imaging (MRI) are useful to differentiate HFS from other facial movement disorders and for intraoperative planning. The standard medical management for HFS is botulinum neurotoxin (BoNT) injections, which provides low-risk but limited symptomatic relief. The only curative treatment for HFS is microvascular decompression (MVD), a surgical intervention that provides lasting symptomatic relief by reducing compression of the facial nerve root. With a low rate of complications such as hearing loss, MVD remains the treatment of choice for HFS patients as intraoperative technique and monitoring continue to improve.