Coerced consent in clinical research: study protocol for a randomized controlled trial.

BACKGROUND: Despite the low-risk nature of participation in most clinical anesthesia trials, subject recruitment on the same day as surgery is often restricted due to the concerns of researchers and local research ethics boards that same-day consent may not afford adequate time and opportunity for patients to weigh and make decisions, as well as perceptions of patient vulnerability immediately prior to surgery that could impact the voluntary nature and the rigor of the informed consent process. However, specialties such as anesthesiology, critical care, interventional radiology, and emergency medicine have a varied pattern of practice and patient acquaintance that does not typically afford the luxury of time or, in many cases, advance consent for participation in research. Indeed, the initial encounter between anesthesiologists and patients undergoing elective procedures routinely occurs on the day of surgery. Concerns of coercion related to same-day consent for clinical anesthesia research trials have not been borne out in the literature, and represent a significant obstacle to clinical researchers, as well as to the patients who are denied opportunities for potential benefit through participation in research studies. METHODS: We describe the protocol for a prospective randomized controlled trial examining the voluntariness of patient consent, solicited either in advance of surgery or on the same day, to participate in an anesthesia research study at Women's College Hospital. One hundred fourteen patients scheduled to undergo ambulatory anterior cruciate ligament repair facilitated by general anesthesia with an adductor canal block will be randomized for recruitment either (a) in the pre-operative assessment clinic before the day of surgery or (b) on the day of surgery, to be approached for consent to participate in a fabricated research study of adjunct medications in adductor canal blocks. Regardless of allocation, patients in both groups will receive the same routine standard of care and will complete a post-operative questionnaire to signal perceptions of undue influence in the process of providing informed consent for the fabricated trial. DISCUSSION: This study will inform trial design and practice guidelines surrounding the amount of time patients ought to be afforded in order to make durable decisions to participate (or not) in clinical research studies. This is expected to impact trial recruitment in a variety of clinical settings where researchers have only brief opportunities to interface with patients. TRIAL REGISTRATION: The trial was registered prospectively on the Open Science Framework (OSF), registration #46twc, on 2023-Mar-17.

Auditory oddball responses in the human subthalamic nucleus and substantia nigra pars reticulata.

The auditory oddball is a mainstay in research on attention, novelty, and sensory prediction. How this task engages subcortical structures like the subthalamic nucleus and substantia nigra pars reticulata is unclear. We administered an auditory OB task while recording single unit activity (35 units) and local field potentials (57 recordings) from the subthalamic nucleus and substantia nigra pars reticulata of 30 patients with Parkinson's disease undergoing deep brain stimulation surgery. We found tone modulated and oddball modulated units in both regions. Population activity differentiated oddball from standard trials from 200 ms to 1000 ms after the tone in both regions. In the substantia nigra, beta band activity in the local field potential was decreased following oddball tones. The oddball related activity we observe may underlie attention, sensory prediction, or surprise-induced motor suppression.

Axial Impairment Following Deep Brain Stimulation in Parkinson's Disease: A Surgicogenomic Approach.

BACKGROUND: Postoperative outcome following deep brain stimulation (DBS) of the subthalamic nucleus is variable, particularly with respect to axial motor improvement. We hypothesized a genetic underpinning to the response to surgical intervention, termed "surgicogenomics". OBJECTIVE: We aimed to identify genetic variants associated with clinical heterogeneity in DBS outcome of Parkinson's disease (PD) patients that could then be applied clinically to target selection leading to improved surgical outcome. METHODS: Retrospective clinical data was extracted from 150 patient's charts. Each individual was genotyped using the genome-wide NeuroX array tailored to study neurologic diseases. Genetic data were clustered based on surgical outcome assessed by comparing pre- and post-operative scores of levodopa equivalent daily dose and axial impairment at one and five years post-surgery. Allele frequencies were compared between patients with excellent vs. moderate/poor outcomes grouped using a priori defined cut-offs. We analyzed common variants, burden of rare coding variants, and PD polygenic risk score. RESULTS: NeuroX identified 2,917 polymorphic markers at 113 genes mapped to known PD loci. The gene-burden analyses of 202 rare nonsynonymous variants suggested a nominal association of axial impairment with 14 genes (most consistent with CRHR1, IP6K2, and PRSS3). The strongest association with surgical outcome was detected between a reduction in levodopa equivalent daily dose and common variations tagging two linkage disequilibrium blocks with SH3GL2. CONCLUSION: Once validated in independent populations, our findings may be implemented to improve patient selection for DBS in PD.

Neurophysiological responses of globus pallidus internus during the auditory oddball task in Parkinson's disease.

Parkinson's disease can be associated with significant cognitive impairment that may lead to dementia. Deep brain stimulation (DBS) of the subthalamic nucleus is an effective therapy for motor symptoms but is associated with cognitive decline. DBS of globus pallidus internus (GPi) poses less risk of cognitive decline so may be the preferred target. A research priority is to identify biomarkers of cognitive decline in this population, but efforts are hampered by a lack of understanding of the role of the different basal ganglia nuclei, such as the globus pallidus, in cognitive processing. During deep brain stimulation (DBS) surgery, we monitored single units, beta oscillatory LFP activity as well as event related potentials (ERPs) from the globus pallidus internus (GPi) of 16 Parkinson's disease patients, while they performed an auditory attention task. We used an auditory oddball task, during which one standard tone is presented at regular intervals and a second deviant tone is presented with a low probability that the subject is requested to count and report at the end of the task. All forms of neuronal activity studied were selective modulated by the attended tones. Of 62 neurons studied, the majority (51 or 82%) responded selectively to the deviant tone. Beta oscillatory activity showed an overall desynchronization during both types of attended tones interspersed by bursts of beta activity giving rise to peaks at a latency of around 200 ms after tone onset. cognitive ERPs recorded in GPi were selective to the attended tone and the right-side cERP was larger than the left side. The averages of trials showing a difference in beta oscillatory activity between deviant and standard also had a significant difference in cERP amplitude. In one block of trials, the random occurrence of 3 deviant tones in short succession silenced the activity of the GPi neuron being recorded. Trial blocks where a clear difference in LFP beta was seen were twice as likely to yield a correct tone count (25 vs 11). The data demonstrate strong modulation of GPi neuronal activity during the auditory oddball task. Overall, this study demonstrates an involvement of GPi in processing of non-motor cognitive tasks such as working memory and attention, and suggests that direct effects of DBS in non-motor GPi may contribute to cognitive changes observed post-operatively.

Say what? Patients have poor immediate memory of major risks of interscalene block disclosed during the informed consent discussion.

BACKGROUND: Poor memory of disclosed risks can undermine informed consent and create medicolegal challenges. The extent to which patients remember the risks of peripheral nerve blockade following the informed consent discussion is unknown. This prospective cohort study evaluated patients' immediate memory of risks related to interscalene block (ISB) that were disclosed during the preoperative informed consent discussion. METHODS: Using a standardized script, patients scheduled for arthroscopic shoulder surgery were informed of the risks of ISB by an anesthesiologist in the preoperative assessment clinic. Immediately thereafter, consenting participants were asked to identify the risks of ISB from a printed list of nine true risks (four major and five minor) and nine 'distractor' items, which were unrelated adverse events and not disclosed. The primary outcome was the proportion of participants who remembered all four true major risks including long-term nerve damage, seizure, life-threatening event, and damage to the covering of the lung. RESULTS: Among 125 participants, only 26 (21%) remembered all four major risks of ISB. The mean number of major risks remembered was 2±1 out of 4. Fifteen (12%) participants remembered all nine true risks. The mean number of true risks remembered was 6±2 out of 9. Multivariable analysis revealed that participants' self-rated assessment of their memory was not associated with actual recall. CONCLUSION: Patients have poor immediate memory of the major risks related to ISB disclosed during the informed consent discussion. Under the present study conditions, the validity of the informed consent process for patients undergoing ISB may be undermined.

Intracarotid etomidate is a safe alternative to sodium amobarbital for the Wada test.

BACKGROUND: The Wada procedure (the intracarotid amobarbital procedure) has been used widely to evaluate the hemispheric dominance of language and memory before temporal lobe surgery in patients with medically refractory seizures. Because of repeated shortage of sodium amobarbital, attempts have been made to find a suitable alternative to sodium amobarbital. The aim of our study was to review our experience with the use of etomidate as an alternative to sodium amobarbital for Wada testing in patients with medically refractory seizures. METHODS: After the ethics approval, we retrospectively reviewed the charts of 29 consecutive patients who underwent Wada test with etomidate. Data from a total of 50 hemispheric injections were reviewed and analyzed. This included the electroencephalographic and motor effects of etomidate injection and their time course (onset and recovery), Wada test results (language laterality and memory performance), and all adverse events during the procedure. RESULTS: Intracarotid administration of etomidate produced a predictable electroencephalographic and motor effects in all patients. The desirable effect was seen with a single bolus dose of 2 mg followed by an infusion. Shivering was the most common side effect, seen in all the patients. Successful testing was possible in nearly all patients without any major side effects. The "pass rate" of valid tests was in good accord with our previous experience with the use of sodium amobarbital. CONCLUSION: From our experience, etomidate is a safe alternative to sodium amobarbital for the Wada test for determining the hemispheric dominance for speech and in predicting the memory outcome.

Default mode network connectivity indicates episodic memory capacity in mesial temporal lobe epilepsy.

PURPOSE: The clinical relevance of resting state functional connectivity in neurologic disorders, including mesial temporal lobe epilepsy (mTLE), remains unclear. This study investigated how connectivity in the default mode network changes with unilateral damage to one of its nodes, the hippocampus (HC), and how such connectivity can be exploited clinically to characterize memory deficits and indicate postsurgical memory change. METHODS: Functional magnetic resonance imaging (fMRI) resting state scans and neuropsychological memory assessments (Warrington Recognition Tests for Words and Faces) were performed on 19 healthy controls, 20 patients with right mTLE, and 18 patients with left mTLE. In addition, postsurgical fMRI resting state and memory change (postsurgical memory performance-presurgical memory performance) data were available for half of these patients. KEY FINDINGS: Patients with mTLE showed reduced connectivity from the posterior cingulate cortex (PCC) to the epileptogenic HC and increased PCC connectivity to the contralateral HC. Stronger PCC connectivity to the epileptogenic HC was associated with better presurgical memory and with greater postsurgical memory decline. Stronger PCC connectivity to the contralateral HC was associated with less postsurgical memory decline. Following surgery, PCC connectivity to the remaining HC increased from presurgical values and showed enhanced correlation with postsurgical memory function. It is notable that this index was superior to others (hippocampal volume, preoperative memory scores) in explaining variance in memory change following surgery. SIGNIFICANCE: Our results demonstrate the striking clinical significance of the brain's intrinsic connectivity in evaluating cognitive capacity and indicating the potential of postsurgical cognitive morbidity in patients with mTLE.

Neuropsychology in temporal lobe epilepsy: influences from cognitive neuroscience and functional neuroimaging.

Neuropsychologists assist in diagnosis (i.e., localization of dysfunction) and in prediction (i.e., how cognition may change following surgery) in individuals being considered for temporal lobe surgery. The current practice includes behavioural testing as well as mapping function via stimulation, inactivation, and (more recently) functional imaging. These methods have been providing valuable information in surgical planning for 60 years. Here, we discuss current assessment strategies and highlight how they are evolving, particularly with respect to integrating recent advances in cognitive neuroscience.