Cortical oscillations play a fundamental role in organizing large-scale functional brain networks. Noninvasive brain stimulation with temporally patterned waveforms such as repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) have been proposed to modulate these oscillations. Thus, these stimulation modalities represent promising new approaches for the treatment of psychiatric illnesses in which these oscillations are impaired. However, the mechanism by which periodic brain stimulation alters endogenous oscillation dynamics is debated and appears to depend on brain state. Here, we demonstrate with a static model and a neural oscillator model that recurrent excitation in the thalamo-cortical circuit, together with recruitment of cortico-cortical connections, can explain the enhancement of oscillations by brain stimulation as a function of brain state. We then performed concurrent invasive recording and stimulation of the human cortical surface to elucidate the response of cortical oscillations to periodic stimulation and support the findings from the computational models. We found that (1) stimulation enhanced the targeted oscillation power, (2) this enhancement outlasted stimulation, and (3) the effect of stimulation depended on behavioral state. Together, our results show successful target engagement of oscillations by periodic brain stimulation and highlight the role of nonlinear interaction between endogenous network oscillations and stimulation. These mechanistic insights will contribute to the design of adaptive, more targeted stimulation paradigms.

Summary:Purpose: Focal cortical dysplasia (CD) is increasingly recognized as a common pathologic substrate of medically intractable epilepsy. As these lesions are often localized in the frontal lobe (therefore in potentially eloquent cortex), an understanding of the functional status of the involved region(s) and of its anatomic and pathologic correlates is of prime importance. The purpose of this study is to assess the function of focal CD in relation to magnetic resonance imaging (MRI) and histopathologic features.Methods: Eight patients operated on for medically intractable epilepsy with histologically proven focal CD involving putative eloquent cortex in the frontal lobe (perirolandic and Broca's areas) were included in the study. Functional regions (motor and language) and epileptogenic areas were assessed by extraoperative electrocorticographic recording and electrical cortical mapping. Cortical functions were correlated with the extent of epileptogenicity on electrocorticographic recordings, MRI features, and histologic characteristics.Results: Language or motor areas were colocalized with epileptogenic regions (n ‫ס‬ 6 of 8, 75%), but were not mapped in regions of increased signal on fluid-attenuated inversion recovery (FLAIR) MRI (when they were identified) on preoperative MRI (n ‫ס‬ 5 of 5, 100%). Histologically, balloon cells were almost exclusively found in nonfunctional regions with FLAIR MRI abnormalities. When resected, regions of motor cortex were characterized by cortical dyslamination, columnar disorganization, and dysmorphic neurons, but were devoid of balloon cells. Conclusions:We found an absence of language or motor functions in perirolandic and Broca's areas that showed decreased epileptogenicity, histopathological evidence of CD with balloon cells and FLAIR MRI signal increase. Language and motor functions were present in epileptogenic and dysplastic areas with no balloon cells and no FLAIR signal abnormalities. These findings have implications on options for epilepsy surgery in patients with CD.

Object Decompressive laminectomy for stenosis is the most common operation performed on the lumbar spine in older patients. This prospective study was designed to evaluate long-term results in patients with symptomatic lumbar stenosis. Methods Between January 1984 and January 1995, 170 patients underwent surgery for lumbar stenosis (86 patients), lumbar stenosis and herniated disc (61 patients), or lateral recess stenosis (23 patients). The male/female ratio for each group was 43:43, 39:22, and 14:9, respectively. The average age for all groups was 61.4 years. For patients with lumbar stenosis, the success rate was 88.1% at 6 weeks and 86.7% at 6 months. For patients with lumbar stenosis and herniated disc, the success rate was 80% at 6 weeks and 77.6% at 6 months, with no statistically significant difference between the two groups. For patients with lateral recess stenosis, the success rate was 58.7% at 6 weeks and 63.6% at 6 months; however, the sample was not large enough to be statistically significant. One year after surgery a questionnaire was sent to all patients; 163 (95.9%) responded. The success rate in patients with stenosis had declined to 69.6%, which was significant (p = 0.012); the rate for patients with stenosis and herniated disc was 77.2%; and that for lateral recess stenosis was 65.2%. Another follow-up questionnaire was sent to patients 1 to 11 years after surgery (average 5.1 years); 146 patients (85.9%) responded, 10 (5.9%) were deceased, and 14 (8.2%) were lost to follow-up review. At 1 to 11 years the success rate was 70.8% for patients with stenosis, 66.6% for those with stenosis and herniated disc, and 63.6% for those with lateral recess stenosis. Eleven patients who underwent reoperation were included in the group of patients whose surgeries proved unsuccessful, regardless of their ultimate outcome. There was no statistically significant difference in outcome between 1 year and 1 to 11 years with respect to stenosis, stenosis with herniated disc, and lateral recess stenosis. Conclusions In conclusion, long-term improvement after laminectomy was maintained in two-thirds of these patients.

Our initial hybrid PET-MRI experience increased diagnostic yields for detection of potential epileptic lesions. This may be due to the unique advantage of improved co-registration and simultaneous review of both structural and functional data.

Objective To describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain‐responsive neurostimulator (RNS) system. Methods We retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3‐month follow‐up after MTL resection compared to seizure frequency 3 months before MTL resection. Results We identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty‐five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (mean = 42 months ICEEG); follow‐up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow‐up was 100% (mean: 94%; range: 50%‐100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure‐free at last follow‐up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%‐100%) at last follow‐up, with eight of fifteen seizure‐free. For those with more than 1 year of follow‐up (N = 21), 15 patients (71%) were seizure‐free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets. Significance Chronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.