Joshua L. Dowling

Cortical and subcortical blood flow effects of subthalamic nucleus stimulation in PD

Objective: To assess whether subthalamic nuclei (STN) stimulation’s primary mechanism of action is to drive or inhibit output neurons. Methods: Cerebral blood flow responses to STN stimulation were measured using PET in 13 patients with Parkinson disease. Patients were scanned with stimulators off and on (six scans each condition). Clinical ratings, EMG, and videotaping of movements were obtained at each scan. Scans with observable tremor or movement were eliminated from analysis. Brain regions where STN stimulation significantly altered blood flow were identified. Results: STN stimulation increased blood flow in midbrain (including STN), globus pallidus, and thalamus, primarily on the left side, but reduced blood flow bilaterally in frontal, parietal, and temporal cortex. Conclusions: These data suggest that STN stimulation increases firing of STN output neurons, which increases inhibition of thalamocortical projections, ultimately decreasing blood flow in cortical targets. STN stimulation appears to drive, rather than inhibit, STN output neurons.

Stimulation of STN impairs aspects of cognitive control in PD

Objective: To test the hypothesis that subthalamic nucleus (STN) stimulation in Parkinson disease (PD) patients affects working memory and response inhibition performance, particularly under conditions of high demand on cognitive control. Methods: To test this hypothesis, spatial working memory (spatial delayed response [SDR]) and response inhibition (Go–No–Go [GNG]) tasks requiring varying levels of cognitive control were administered to patients with PD with previously implanted bilateral STN stimulators (n = 24). Patients did not take PD medications overnight. Data were collected while bilateral stimulators were on and off, counterbalancing the order across subjects. Results: On the SDR task, STN stimulation decreased patients’ working memory performance under a high but not low memory load condition (effect of stimulator condition on high load only and condition × load interaction, p < 0.05). On the GNG task, STN stimulation reduced discriminability on a high but not medium inhibition condition (effect of stimulator condition on high inhibition level only, p = 0.05; condition × inhibition level interaction, p = 0.07). Conclusion: STN stimulation reduces working memory and response inhibition performance under conditions of greater challenge to cognitive control despite significant improvement of motor function.

Electrocorticographic Frequency Alteration Mapping: A Clinical Technique for Mapping the Motor Cortex

OBJECTIVE Electrocortical stimulation (ECS) has been well established for delineating the eloquent cortex. However, ECS is still coarse and inefficient in delineating regions of the functional cortex and can be hampered by after-discharges. Given these constraints, an adjunct approach to defining the motor cortex is the use of electrocorticographic signal changes associated with active regions of the cortex. The broad range of frequency oscillations are categorized into two main groups with respect to the sensorimotor cortex: low and high frequency bands. The low frequency bands tend to show a power reduction with cortical activation, whereas the high frequency bands show power increases. These power changes associated with the activated cortex could potentially provide a powerful tool in delineating areas of the motor cortex. We explore electrocorticographic signal alterations as they occur with activated regions of the motor cortex, as well as its potential in clinical brain mapping applications. METHODS We evaluated seven patients who underwent invasive monitoring for seizure localization. Each patient had extraoperative ECS mapping to identify the motor cortex. All patients also performed overt hand and tongue motor tasks to identify associated frequency power changes in regard to location and degree of concordance with ECS results that localized either hand or tongue motor function. RESULTS The low frequency bands had a high sensitivity (88.9–100%) and a lower specificity (79.0–82.6%) for identifying electrodes with either hand or tongue ECS motor responses. The high frequency bands had a lower sensitivity (72.7–88.9%) and a higher specificity (92.4–94.9%) in correlation with the same respective ECS positive electrodes. CONCLUSION The concordance between stimulation and spectral power changes demonstrate the possible utility of electrocorticographic frequency alteration mapping as an adjunct method to improve the efficiency and resolution of identifying the motor cortex.

Safety and efficacy of subthalamic nucleus deep brain stimulation performed with limited intraoperative mapping for treatment of Parkinson's disease.

OBJECTIVE The aim of this study is to establish the safety and efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinsons disease (PD) patients with disabling motor fluctuations performed with an expedient procedure with limited intraoperative mapping. METHODS Bilateral STN DBS systems were implanted in 110 PD patients. Targeting of STN was achieved with T2-weighted magnetic resonance imaging guidance and a stereotactic navigation system confirmed by limited electrophysiological mapping. The safety of the procedure was analyzed in all 110 patients. The efficacy of the procedure was assessed in the practically-defined off medication state in the 72 patients who underwent evaluations 3 to 12 months after electrode implantation. RESULTS Adverse effects were infrequent and transient with no incidence of death, hemiparesis, or seizure. In the 72 patients, STN DBS reduced total Unified Parkinsons Disease Rating Scale motor scores at the time of the follow-up evaluation by 47% from 43.4 ± 16.1 with stimulators off to 22.8 ± 11.6 with stimulators on (P < 0.001). The changes in Unified Parkinsons Disease Rating Scale motor subscores improved as follows: rest tremor, 74% (P < 0.001); rigidity, 58% (P < 0.001); bradykinesia, 37% (P < 0.001); pull test, 35% (P < 0.001); gait, 44% (P < 0.001); axial signs, 42% (P < 0.001); and speech, 13% (P = 0.002). The prescribed total daily levodopa-equivalent dose decreased 45 ± 32%. We averaged 1.3 ± 0.9 electrodes passes per lead implantation. The mean operating time from the mounting of the stereotactic frame to its removal was 5 hours 42 minutes (median, 5 h 25 min; standard deviation, 1 h 12 min). CONCLUSION This STN DBS surgical technique for PD is expedient with effective outcomes and low complication rates.

Combined surgical resection and stereotactic radiosurgery for treatment of cerebral metastases

BACKGROUND Patients with limited intracranial metastatic disease traditionally have been treated with surgery followed by WBRT. However, there is growing concern for the debilitating cognitive effects after WBRT in long-term survivors. We present a series of patients treated with surgery followed by SRS, while reserving WBRT as a salvage therapy for disease progression. METHODS Medical records from 15 patients with 1 to 2 cerebral metastases who underwent both resection and SRS were reviewed. Outcome measures included overall survival, survival by RPA class, EOR, local tumor control, progression of intracranial disease, need for WBRT salvage therapy, and COD. RESULTS Fifteen patients with cerebral metastases were treated with the combined surgery-SRS paradigm. Eight of the 15 patients (53.3%) were designated RPA class 1, with 6 of 15 (40.0%) in class 2 and 1 of 15 (6.7%) in class 3. Gross total resection was achieved in 12 cases (80.0%). Overall median survival was 20.0 months, with values of 22.0 and 13.0 months for RPA classes 1 and 2, respectively. Local recurrence occurred in 16.7% of those patients with GTR. Six patients (40.0%) went on to receive WBRT at a median of 8.0 months from initial presentation. Twelve patients (80.0%) had died at the completion of the study, and the COD was CNS progression in 33.3%. CONCLUSIONS Surgical resection combined with SRS is an effective treatment for selected patients with limited cerebral metastatic disease. Survival using this combined treatment was equivalent to or greater than that reported by other studies using surgery + WBRT or SRS + WBRT.

LCBF changes in rat somatosensory cortex during whisker stimulation monitored by dynamic H2 clearance

We evaluated increases in local cerebral blood flow (LCBF) localized to single activated cortical columns by H2 clearance methods. The rat whisker-barrel cortex is a model for cortical function and neural processing in active explorative behaviors. Up to four 30-40 microns Pt wire electrodes were inserted in or near the rat whisker-barrel cortex. Electrode positions were mapped by postmortem histology. H2 was generated electrochemically by constant current from one electrode and detected by one or more other electrodes 300-500 microns away. Changes in LCBF produced inverse changes in PH2. Shifts during steady H2 generation were calibrated against standard H2 inhalation clearance curves at rest and during inhalation of 7.5% CO2 for 1 min for quantitative estimates of LCBF. Contralateral whisker stimulation at 3 Hz, 1 min duration and delivered every 2 min produced the largest increases in LCBF. LCBF responses were detected in approximately 1 s. Stimulation of single whiskers produced the largest responses when an electrode was in the corresponding barrel. These results indicate that increased neural activity in a single cortical column produces blood flow responses primarily in that column.

Management of atypical cranial meningiomas, part 1: predictors of recurrence and the role of adjuvant radiation after gross total resection.

BACKGROUND Indications for external beam radiation therapy (EBRT) for atypical meningiomas (AMs) remain unclear. OBJECTIVE To analyze features associated with recurrence in AM patients after gross total resection (GTR) and to assess the relative benefit of EBRT in a retrospective cohort study. METHODS One hundred fifty-one primary AMs after GTR (88 female patients; median follow-up, 45.0 months) were examined for possible predictors of recurrence (age, sex, location, volume, bone involvement, brain invasion). The Fisher exact and Wilcoxon rank-sum tests were used to analyze the association between these predictors and use of EBRT. The impact on recurrence for these predictors and EBRT was analyzed with Kaplan-Meier and Cox regression. RESULTS Of 151 patients, 13 (8.6%) experienced recurrence after GTR (median, 47.0 months). Multivariate analysis identified elevated mitotic index (P = .007) and brain invasion (P = .002) as predictors of recurrence. Larger volume (P = .96) was not associated with recurrence but was more likely to prompt EBRT (P = .001). Recurrences occurred in 11 of 112 with GTR (9.8%; median, 44 months) and 2 of 39 with GTR/EBRT (5.1%; median, 133 months). The 2-, 5-, and 10-year progression-free survival rates after GTR vs GTR/EBRT were 97%, 86%, and 68% vs 100%, 100%, and 78%. Kaplan-Meier analysis demonstrated no difference in progression-free survival or overall survival after GTR vs GTR/EBRT (P = .8, P > .99). CONCLUSION Brain invasion and high mitotic rates may predict recurrence. After GTR of AMs, EBRT appears not to affect progression-free survival and overall survival, suggesting that observation rather than EBRT may be indicated after GTR.

Correlation of Severity of FDG-PET Hypometabolism and Interictal Regional Delta Slowing in Temporal Lobe Epilepsy

Summary:  Purpose: We investigated the association of severity of hypometabolism detected by positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) and persistence of interictal EEG focal slowing in patients with refractory temporal lobe epilepsy.

Thalamic stimulation for primary writing tremor

Abstract We report a patient with primary writing tremor whose tremor was treated with thalamic stimulation. He had undergone trials of multiple oral medications with no benefit for his tremor. An electrode lead was implanted in the thalamic nucleus ventralis intermedius with nearly complete control of his tremor and no postoperative complications. We conclude that nucleus ventralis intermedius thalamic stimulation is safe and effective for primary writing tremor.

Wada Testing Reveals Frontal Lateralization for the Memorization of Words and Faces

Neuroimaging studies have suggested that specific regions of the frontal and medial temporal cortex are engaged during memory formation. Further, there is specialization across these regions such that verbal materials appear to preferentially engage the left regions while nonverbal materials primarily engage the right regions. An open question, however, has been to what extent frontal regions contribute to successful memory formation. The present study investigates this question using a reversible lesion technique known as the Wada test. Patients memorized words and unfamiliar faces while portions of their left and right hemispheres were temporarily anesthetized with sodium amytal. Subsequent memory tests revealed that faces were remembered better than words following left-hemisphere anesthesia, whereas words were remembered better than faces following right-hemisphere anesthesia. Importantly, inspection of the circulation affected by the amytal further suggests that these memory impairments did not result from direct anesthetization of the medial temporal regions. Taken in the context of the imaging findings, these results suggest that frontal regions may also contribute to memory formation in normal performance.