02491nas a2200229 4500008004100000022001400041245013500055210006900190260000900259300001200268490000600280520167600286100002301962700001801985700003402003700002102037700002102058700001902079700002702098700001802125856011802143 2024 eng d a2632-129700aThe involvement of the piriform cortex in non-lesional temporal lobe epilepsy: an uncommon component of the epileptogenic network.0 ainvolvement of the piriform cortex in nonlesional temporal lobe  c2024 afcae1790 v63 a

The piriform cortex is recognized as highly epileptogenic in rodents, yet its electrophysiological role in human epilepsy remains understudied. Recent surgical outcomes have suggested potential benefits in resecting the piriform cortex for cases of medial temporal lobe epilepsy. However, little is known about its electrophysiological activity in human epilepsy. This case-series study aimed to explore the electrophysiological role of the piriform cortex within the epileptogenic network among patients with suspected temporal lobe epilepsy. Participants were recruited from Emory University Hospital or Children's Healthcare of Atlanta, with non-lesional frontotemporal or temporal lobe hypotheses, undergoing stereoelectroencephalographic studies. Specifically, focus was placed on patients with one or more electrode contacts in the piriform cortex. Primary objectives included determining piriform cortex involvement within the electrophysiologically defined epileptogenic network and assessing the effects of electrical stimulation. Twenty-two patients were included in the study. Notably, only one patient exhibited piriform cortex involvement at seizure onset, associated with an olfactory aura. Two patients showed early piriform cortex involvement, while others displayed late or no involvement. Electrical stimulation of the piriform cortex induced after-discharges in three patients and replicated a habitual seizure in one. These findings present a contrast to surgical outcome studies, suggesting that the piriform cortex may not typically play a significant role in the epileptogenic network among patients with non-lesional temporal lobe epilepsy.

1 aPedersen, Nigel, P1 aRaghu, Ashley1 aShivamurthy, Veeresh, Kumar N1 aChern, Joshua, J1 aGross, Robert, E1 aWillie, Jon, T1 aDingledine, Raymond, J1 aKheder, Ammar uhttps://www.neurotechcenter.org/publications/2024/involvement-piriform-cortex-non-lesional-temporal-lobe-epilepsy02594nas a2200325 4500008004100000022001400041245010900055210006900164260001600233300000900249490000700258520156700265653001001832653002301842653002701865653002401892653001301916653001101929653001801940100002101958700001801979700001601997700001902013700002502032700002102057700002302078700001902101700002502120856012302145 2024 eng d a2041-172300aMultisensory flicker modulates widespread brain networks and reduces interictal epileptiform discharges.0 aMultisensory flicker modulates widespread brain networks and red c2024 Apr 11 a31560 v153 a

Modulating brain oscillations has strong therapeutic potential. Interventions that both non-invasively modulate deep brain structures and are practical for chronic daily home use are desirable for a variety of therapeutic applications. Repetitive audio-visual stimulation, or sensory flicker, is an accessible approach that modulates hippocampus in mice, but its effects in humans are poorly defined. We therefore quantified the neurophysiological effects of flicker with high spatiotemporal resolution in patients with focal epilepsy who underwent intracranial seizure monitoring. In this interventional trial (NCT04188834) with a cross-over design, subjects underwent different frequencies of flicker stimulation in the same recording session with the effect of sensory flicker exposure on local field potential (LFP) power and interictal epileptiform discharges (IEDs) as primary and secondary outcomes, respectively. Flicker focally modulated local field potentials in expected canonical sensory cortices but also in the medial temporal lobe and prefrontal cortex, likely via resonance of stimulated long-range circuits. Moreover, flicker decreased interictal epileptiform discharges, a pathological biomarker of epilepsy and degenerative diseases, most strongly in regions where potentials were flicker-modulated, especially the visual cortex and medial temporal lobe. This trial met the scientific goal and is now closed. Our findings reveal how multi-sensory stimulation may modulate cortical structures to mitigate pathological activity in humans.

10aBrain10aCross-Over Studies10aElectroencephalography10aEpilepsies, Partial10aEpilepsy10aHumans10aTemporal Lobe1 aBlanpain, Lou, T1 aCole, Eric, R1 aChen, Emily1 aPark, James, K1 aWalelign, Michael, Y1 aGross, Robert, E1 aCabaniss, Brian, T1 aWillie, Jon, T1 aSinger, Annabelle, C uhttps://www.neurotechcenter.org/publications/2024/multisensory-flicker-modulates-widespread-brain-networks-and-reduces02036nas a2200193 4500008004100000245011900041210006900160260001200229520131200241100002101553700001601574700001601590700002501606700002101631700002301652700001901675700002501694856012301719 2023 eng d00aMultisensory Flicker Modulates Widespread Brain Networks and Reduces Interictal Epileptiform Discharges in Humans.0 aMultisensory Flicker Modulates Widespread Brain Networks and Red c03/20233 a

Modulating brain oscillations has strong therapeutic potential. However, commonly used non-invasive interventions such as transcranial magnetic or direct current stimulation have limited effects on deeper cortical structures like the medial temporal lobe. Repetitive audio- visual stimulation, or sensory flicker, modulates such structures in mice but little is known about its effects in humans. Using high spatiotemporal resolution, we mapped and quantified the neurophysiological effects of sensory flicker in human subjects undergoing presurgical intracranial seizure monitoring. We found that flicker modulates both local field potential and single neurons in higher cognitive regions, including the medial temporal lobe and prefrontal cortex, and that local field potential modulation is likely mediated via resonance of involved circuits. We then assessed how flicker affects pathological neural activity, specifically interictal epileptiform discharges, a biomarker of epilepsy also implicated in Alzheimer’s and other diseases. In our patient population with focal seizure onsets, sensory flicker decreased the rate interictal epileptiform discharges. Our findings support the use of sensory flicker to modulate deeper cortical structures and mitigate pathological activity in humans.

1 aBlanpain, Lou, T1 aChen, Emily1 aPark, James1 aWalelign, Michael, Y1 aGross, Robert, E1 aCabaniss, Brian, T1 aWillie, Jon, T1 aSinger, Annabelle, C uhttps://www.neurotechcenter.org/publications/2023/multisensory-flicker-modulates-widespread-brain-networks-and-reduces02781nas a2200349 4500008004100000022001400041245012100055210006900176260001200245300001200257490000700269520164600276100001901922700001701941700002201958700002401980700001802004700002402022700001702046700002502063700001802088700002202106700002102128700002302149700002302172700001902195700002402214700002102238700002402259700002602283856012202309 2023 eng d a2330-161900aPatients with Cognitive Impairment in Parkinson's Disease Benefit from Deep Brain Stimulation: A Case-Control Study.0 aPatients with Cognitive Impairment in Parkinsons Disease Benefit c03/2023 a382-3910 v103 a

BACKGROUND: Deep brain stimulation (DBS) for Parkinson's disease (PD) is generally contraindicated in persons with dementia but it is frequently performed in people with mild cognitive impairment or normal cognition, and current clinical guidelines are primarily based on these cohorts.

OBJECTIVES: To determine if moderately cognitive impaired individuals including those with mild dementia could meaningfully benefit from DBS in terms of motor and non-motor outcomes.

METHODS: In this retrospective case-control study, we identified a cohort of 40 patients with PD who exhibited moderate (two or more standard deviations below normative scores) cognitive impairment (CI) during presurgical workup and compared their 1-year clinical outcomes to a cohort of 40 matched patients with normal cognition (NC). The surgery targeted subthalamus, pallidus or motor thalamus, in a unilateral, bilateral or staged approach.

RESULTS: At preoperative baseline, the CI cohort had higher Unified Parkinson's Disease Rating Scale (UPDRS) subscores, but similar levodopa responsiveness compared to the NC cohort. The NC and CI cohorts demonstrated comparable degrees of postoperative improvement in the OFF-medication motor scores, motor fluctuations, and medication reduction. There was no difference in adverse event rates between the two cohorts. Outcomes in the CI cohort did not depend on the target, surgical staging, or impaired cognitive domain.

CONCLUSIONS: Moderately cognitively impaired patients with PD can experience meaningful motor benefit and medication reduction with DBS.

1 aBlock, Cady, K1 aPatel, Margi1 aRisk, Benjamin, B1 aStaikova, Ekaterina1 aLoring, David1 aEsper, Christine, D1 aScorr, Laura1 aHigginbotham, Lenora1 aAia, Pratibha1 aDeLong, Mahlon, R1 aWichmann, Thomas1 aFactor, Stewart, A1 aYong, Nicholas, Au1 aWillie, Jon, T1 aBoulis, Nicholas, M1 aGross, Robert, E1 aBuetefisch, Cathrin1 aMiocinovic, Svjetlana uhttps://www.neurotechcenter.org/publications/2023/patients-cognitive-impairment-parkinsons-disease-benefit-deep-brain