Brain Network Activity Can Improve in Epilepsy Patients After Surgery

Successful epilepsy surgery can improve brain connectivity similar to patterns seen in people without epilepsy, according to a new study published in the journal Neurosurgery.

The Vanderbilt University Medical Center (VUMC) study of 15 people with temporal lobe epilepsy is the first to show improvements in brain networks after surgery compared to a group of healthy subjects.

Brain networks involved in the study are important for keeping the brain awake and alert, according to senior author Dario Englot, MD, PhD, surgical director of VUMC’s Epilepsy Program.

“It’s important to realize that, over time, seizures lead to brain network problems which may be related to cognitive deficits seen in patients with epilepsy,” said Englot. “Our new results show some brain network activity can improve with surgery if you stop the seizures.”

Neural Stem Cell Transplantation May Reduce Abnormal Increases in New Cells in the Brains of Mice with Temporal Lobe Epilepsy

Featuring the work of former CURE Grantee Dr. Janice Naegele

Adult neurogenesis, a process whereby new neurons are added to the brain, is thought to be confined in mammals to just a few regions, including the hippocampus, a structure important for learning. Whether this process occurs in the adult human brain is controversial, but in most other mammals that have been studied, adult neurogenesis in the hippocampus appears to be essential for forming memories.

Producing new neurons in the adult hippocampus is regulated by the environment, mood, exercise, diet, and disease. In some forms of epilepsy, the production of new cells in the hippocampus, called granule cells, becomes highly abnormal and the altered neurogenesis is thought to increase over-excitation and exacerbate seizures.

In the Naegele laboratory at Wesleyan, researchers are studying whether neural stem cell transplantation can reduce this abnormal adult neurogenesis in mice that have temporal lobe epilepsy. The research is spearheaded by Janice Naegele, the Alan M. Dachs Professor of Science; professor of biology; and professor, neuroscience and behavior.

“Our prior studies in mice with epilepsy showed that transplanting inhibitory neurons from the embryonic mouse brain into the adult mouse hippocampus reorganized neural circuits in the hippocampus and reduced seizures,” Naegele said. “In our most recent study, we asked whether transplanted inhibitory neurons formed functional synaptic connections with adult-born hippocampal neurons generated after the onset of epilepsy.”

The results of that study were published March 27 in eNeuro, an open-access journal of the Society for Neuroscience. The paper is titled “Restrained Dendritic Growth of Adult-born Granule Cells Innervated by Transplanted Fetal GABAergic Interneurons in Mice with Temporal Lobe Epilepsy.

€8 Million Research Project Aims to Develop New Cure for Epilepsy

A new European research project which aims to heal epilepsy by regenerating brain tissue and ‘training’ neurons is getting underway.

The five-year, €8m Hybrid Enhanced Regenerative Medicine Systems project – HERMES, brings together 12 partners from seven EU countries to heal brain disorders using transplants which combine biological and artificial components.

HERMES researchers will study temporal lobe epilepsy, the most common form of epilepsy, which can be resistant to current pharmacological therapies. Temporal lobe epilepsy affects areas of the brain that are involved in learning, memory and emotions, such as the hippocampus.

HERMES will aim to rebuild the part of the hippocampus damaged by this form of epilepsy. Researchers will generate hippocampal tissue in the laboratory and develop a neuromorphic neuroprosthesis – an electronic device that mimics the normal function of the brain’s neurons.

The two components – one biological and the other artificial – will be implanted in the damaged brain area in an animal model with the aim of rebuilding the damaged hippocampus. The neuromorphic neuroprosthesis will be equipped with artificial intelligence to guide the implanted tissue towards the correct integration within the brain.

The device will then serve as a “trainer” for the tissue recreated in the laboratory and will be discontinued upon complete regeneration and functional recovery of the brain area. The new paradigm introduced by HERMES is called enhanced regenerative medicine.

Seizure Control by Low-Intensity Ultrasound in Mice with Temporal Lobe Epilepsy

BACKGROUND: Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. Recent studies have demonstrated that ultrasound stimulation can inhibit spontaneous recurrent seizures and improve behavioral outcomes for rodents with TLE. However, the exact underlying mechanism for inhibition of TLE via ultrasound stimulation remains unknown.

METHODS: In this study, low-intensity pulsed ultrasound stimulation (LIPUS) and low-intensity continuous ultrasound stimulation (LICUS) and concurrent local field potentials (LFPs) in the CA3 field of the hippocampus were recorded in the kainite-induced mouse model of TLE. The power spectrum and the phase-amplitude coupling in the LFPs were quantitatively analyzed.

RESULTS: This study found three significant changes in LFPs after ultrasound stimulation: (i) the intensity of the power spectrum in the low frequency (<10 Hz) was significantly decreased (p < 0.01); (ii) the phase amplitude coupling strength between slow (delta-, theta-, and alpha-frequency bands) and fast (gamma frequency bands) neural oscillations were weakened (p < 0.01); (iii) the interval between seizures was significantly increased (p < 0.01).

CONCLUSIONS: These results indicate that the seizures of temporal lobe epilepsy can be effectively inhibited by ultrasound stimulation, and this effect is independent of ultrasound type (pulsed or continuous).

Using Connectomics to Gain Insight into Epilepsy

Abnormalities in structural brain networks and how brain regions communicate may underlie a variety of disorders, including epilepsy, which is one focus of a two-part Special Issue on the Brain Connectome in Brain Connectivity, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.

This second special issue includes the article entitled “Effective Connectivity within the Default Mode Network in Left Temporal Lobe Epilepsy: Findings from the Epilepsy Connectome Project,” –with results reported from the Epilepsy Connectome Project–contributed by Mary Meyerand, Jeffrey Binder and colleagues from University of Wisconsin-Madison, Medical College of Wisconsin (Milwaukee), and Froedtert Hospital (Milwaukee). Individuals with epilepsy can have memory impairment. Therefore, the researchers studied the default mode network that is a collection of brain regions involved in memory function. The results showed a difference in these memory-related connections between healthy individuals and individuals with epilepsy. The researchers identified an excitatory connection association with inhibition of formation of the left hippocampal region in patients with temporal lobe epilepsy.

The Special Issues were led by Guest Editors Brent Munsell, PhD, College of Charleston (SC), Guorong Wu, PhD, University of North Carolina at Chapel Hill, Leonardo Bonilha, MD, PhD, Medical University of South Carolina (Charleston), and Paul Laurienti, MD, PhD, Wake Forest School of Medicine (Winston-Salem, NC).

Researchers ID Factors Predictive of Naming Decline After Epilepsy Surgery

Paper- and online-based externally validated nomograms are effective in predicting naming decline after temporal lobe surgery in patients with epilepsy, according to study results published in Neurology. Factors predictive of postsurgical naming decline in this patient population included side of surgery, age at epilepsy onset, age at surgery, sex, and education, and preoperative naming score.

A total of 719 patients with epilepsy who underwent temporal lobe epilepsy surgery at the Cleveland Clinic were included in the study. In addition, the investigators enrolled an external validation cohort of 138 patients who also underwent temporal lobe surgery at Columbia University Medical Center, Emory University School of Medicine, or University of Washington School of Medicine.

Groundbreaking Stem Cell Brain Implant Helps Fight Epilepsy in Rats

Severe epilepsy is very difficult to treat, but an experimental approach involving implanted stem cells in the brain represents a groundbreaking way to potentially stop seizures for good.

Carried out by researchers at Texas A&M University, the technique has yet to be tried on human subjects, but has proven highly successful on rats. Rats given the implants suffered 70 percent fewer seizures than those without. That figure could drop further with additional research.

The investigation is the first study of its kind. It demonstrated that grafting certain cells derived from human-induced pluripotent stem cells into the brain can help alleviate seizures, as well as improve brain function. The work targets temporal lobe epilepsy (TLE), the most common type of epilepsy in which seizures originate from the brain’s hippocampus. TLE is a non-genetic form of epilepsy, often resulting from an incident such as a traumatic head injury, brain infections, or fever-related seizures during childhood.

Experiences of Self-Conscious Emotions in Temporal Lobe Epilepsy

Self-conscious emotions (SCEs) with a negative valence (such as shame and guilt) or a positive valence (such as pride) are moral emotions that emerge from self-reflection and self-evaluation processes in social contexts. In some neurologic and psychiatric disorders, experiences of SCEs are dysregulated.

Relative to controls, patients with TLE were more likely to experience negative-valence SCEs to a higher extent and positive SCEs to a lesser extent. The patients who experienced negative-valence SCEs to a higher extent (rather than to a lesser extent) had a higher frequency of seizures, more severe anxiety and depressive symptoms, and a greater prevalence of anxiety and depressive disorders. Furthermore, patients who experienced positive-valence SCEs to a lesser extent (rather than to a higher extent) displayed a higher level of anxiety. Lastly, differences in experiences of SCEs by patients with TLE were associated with a lower quality of life.

In conclusion, experiences of SCEs can be dysregulated in patients with TLE. This dysregulation is linked to the patients’ clinical and psychological symptoms and quality of life. In this context, SCEs might be a target of interest in the management of epilepsy.

Professor Catherine Christian and Jiang Li

Effects of Epilepsy on Neural Activity in Mice Fluctuate with Reproductive Cycle

Mice with epilepsy have altered patterns of neuron activity in the portion of the brain that controls the reproductive endocrine system, University of Illinois researchers report in a new study. Furthermore, the differences in neuron activity in female mice fluctuate across the reproductive cycle, the team found.

The study, which tracked hormone levels and activity in specific neurons that trigger the release of reproductive hormones in mice with epilepsy, demonstrates that the effects of epilepsy on other areas of the brain may not be as static as researchers have thought, said study leader Catherine Christian, a professor of molecular and integrative physiology at Illinois. The study was published in the journal eNeuro. Jiang Li, a graduate student at the University of Illinois, was the lead author of the study.

People with temporal lobe epilepsy – the most common type affecting adults – also have high rates of problems with their reproductive endocrine systems, though the connection is poorly understood.

Theory of Mind Impairment in Focal Versus Generalized Epilepsy

Theory of Mind (ToM) is a critical component of social cognition, and thus, its impairment may adversely affect social functioning and quality of life. Recent evidence has suggested that it is impaired in epilepsy. What is not clear, however, is whether it is related to particular types of epilepsy or other factors.

Researchers undertook this study to explore ToM in patients with focal versus those with generalized epilepsy, the particular pattern of ToM deficits, and the potential influence of antiepileptic medication load. The sample included 149 adults: 79 patients with epilepsy (34 with generalized epilepsy and 45 with focal epilepsy) and 70 healthy controls.

Theory of Mind tasks included:

  1. comprehension of hinting
  2. comprehension of sarcasm and metaphor
  3. comprehension of false beliefs and deception
  4. recognition of faux pas
  5. a visual ToM task in cartoon form

We found significant ToM impairment in the group with focal epilepsy relative to the performance of both the healthy group and the group with generalized epilepsy on all tasks, with the exception of faux pas, on which the group with generalized epilepsy also performed more poorly than the healthy group. Additionally, early age at seizure onset, but not antiepileptic drug (AED) load, was associated with ToM performance.

These findings suggest that focal temporal and frontal lobe, but not generalized, epilepsies were associated with impaired theory of mind. This may reflect the neuroanatomical abnormalities in the relevant neuronal networks and may have implications for differential cognitive-behavioral interventions based on epilepsy type.