Smart needle electrical bioimpedance to provide information on needle tip relationship to target nerve prior to local anesthetic deposition in peripheral nerve block (USgPNB) procedures.

Ultrasound guided peripheral nerve block (USgPNB) refers to anaesthetic techniques to deposit local anesthetic next to nerves, permitting painful surgery without necessitating general anesthesia. Needle tip position prior to local anesthetic deposition is a key determinant of block success and safety. Nerve puncture and intra-neural injection of local anesthetic can cause permanent nerve injury. Currently ultrasound guidance is not sufficiently sensitive to reliably detect needle to nerve proximity. Feedback with bioimpedance data from the smart needle tip might provide the anesthetist with information as to the relationship between the needle tip and the target nerve prior to local anesthetic deposition. Bioimpedance using a smart needle integrated with a two-electrode impedance sensor has been developed to determine needle to nerve proximity during USgPNB. Having obtained all necessary ethical and regulatory approvals, in vivo data on brachial plexus, vagus, femoral and sciatic nerves were obtained from seven pig models using the smart needle bioimpedance system. The excision and histological analysis of above peripheral nerves and observation of the architecture and structure of nerves by means of histology allow the calculation of the ratios of connective tissue to neural tissue to determine the influence of this variable on absolute impedance. The ratio results give extra clinical data and explain the hetrogeneity of impedance data in the pig models and the hypothesis that connective tissue with intra-neural fat has higher impedance than neural tissue.

Association of lifetime major depressive disorder with enhanced attentional sensitivity measured with P3 response in young adult twins.

Major depression is associated with alterations in the auditory P3 event-related potential (ERP). However, the persistence of these abnormalities after recovery from depressive episodes, especially in young adults, is not well known. Furthermore, the potential influence of substance use on this association is poorly understood. Young adult twin pairs (N = 177) from the longitudinal FinnTwin16 study were studied with a psychiatric interview, and P3a and P3b ERPs elicited by task-irrelevant novel sounds and targets, respectively. Dyadic linear mixed-effect models were used to distinguish the effects of lifetime major depressive disorder from familial factors and effects of alcohol problem drinking and tobacco smoking. P3a amplitude was significantly increased and P3b latency decreased, in individuals with a history of lifetime major depression, when controlling the fixed effects of alcohol abuse, tobacco, gender, twins' birth order, and zygosity. These results suggest that past lifetime major depressive disorder may be associated with enhanced attentional sensitivity.

Anesthetic Considerations in Alström Syndrome: A Case Report.

Alström syndrome is a rare genetic condition that affects cardiac, respiratory, endocrine, hepatorenal, gastrointestinal, auditory, ophthalmic, and musculoskeletal systems. This multisystem syndrome poses significant anesthetic challenges, along with a high likelihood of perioperative adverse clinical outcomes. A literature review revealed no reports on the anesthetic management for emergency surgery in adults with Alström syndrome. We report the perioperative management of a patient with Alström syndrome who presented for an emergency laparotomy due to an ischemic bowel. This report highlights perioperative challenges in the management of this condition in the emergency setting.

Chest Wall Regional Anesthesia for Modified Radical Mastectomy and Axillary Lymph Node Dissection: A Case Report.

Restrictive chest wall disorders impair cardiopulmonary physiology and pose anesthesia-related safety challenges. Regional anesthesia, as the primary anesthetic modality, may mitigate general anesthesia-related risks in such patients presenting for breast cancer surgery. We describe the use of chest wall fascial plane blocks as the primary anesthetic, combined with high-flow humidified nasal oxygen and low-dose propofol sedation, in a patient with complex comorbidities presenting for modified radical mastectomy and axillary lymph node dissection.

An investigation of the relationship between glutamate and resting state connectivity in chronic cannabis users.

Human and animal studies have shown that heavy cannabis (CB) use interacts with glutamatergic signaling. Additionally, recent studies have suggested that glutamate (Glu) may drive resting state functional connectivity (RSfc). The aims of the current preliminary study were to: 1) determine whether dorsal anterior cingulate cortex (dACC) Glu is related to RSfc between the dACC and two nodes of the reward network, the nucleus accumbens (NAc) and hippocampus (Hp); and 2) determine whether CB use interacts with the relationship between dACC Glu and RSfc. A group of 23 chronic CB users and 23 healthy controls participated in this multimodal MRI study. Glu levels were assessed in the dACC using magnetic resonance spectroscopy (MRS). Linear regression models were used to determine whether dACC Glu and CB use predicts RSfc between the dACC and the NAc and Hp. While the effect size is small, the results showed that the connectivity between the dACC and right NAc was predicted by the interaction between dACC Glu levels and monthly CB use. Additionally, while there is some suggestion that dACC Glu is correlated with dACC-hippocampal connectivity, unlike for dACC/NAc connectivity the relationship between them does not appear to be affected by CB use. These preliminary findings are significant in that they demonstrate the need for future studies with larger sample sizes to better characterize the relationship between resting state connectivity and neurochemistry as well as to characterize how CB use interacts with that relationship.

Disturbances of postural sway components in cannabis users.

INTRODUCTION: A prominent effect of acute cannabis use is impaired motor coordination and driving performance. However, few studies have evaluated balance in chronic cannabis users, even though density of the CB1 receptor, which mediates the psychoactive effects of cannabis, is extremely high in brain regions critically involved in this fundamental behavior. The present study measured postural sway in regular cannabis users and used rambling and trembling analysis to quantify the integrity of central and peripheral nervous system contributions to the sway signal. METHODS: Postural sway was measured in 42 regular cannabis users (CB group) and 36 non-cannabis users (N-CB group) by asking participants to stand as still as possible on a force platform in the presence and absence of motor and sensory challenges. Center of pressure (COP) path length was measured, and the COP signal was decomposed into rambling and trembling components. Exploratory correlational analyses were conducted between sway variables, cannabis use history, and neurocognitive function. RESULTS: The CB group had significantly increased path length and increased trembling in the anterior-posterior (AP) direction. Exploratory correlational analyses suggested that AP rambling was significantly inversely associated with visuo-motor processing speed. DISCUSSION: Regular cannabis use is associated with increased postural sway, and this appears to be predominantly due to the trembling component, which is believed to reflect the peripheral nervous system's contribution to the sway signal.

A cross-sectional survey of anaesthesia-related expectations amongst patients awaiting upper limb trauma surgery.

BACKGROUND AND AIMS: Little is known regarding patients' anaesthesia-related expectations when presenting for upper limb trauma surgery. METHODS: We conducted a prospective cross-sectional survey exploring prior anaesthetic experience, anaesthesia-related knowledge, anaesthesia expectations, the preoperative visit and factors likely to influence anaesthesia choice. The survey was completed by 192 patients. RESULTS: Anaesthetists were identified as doctors by 52%; 53% were unaware of their planned anaesthesia; 58% indicated likely acceptance of regional anaesthesia. Information regarding anaesthesia originated mostly from surgeons (65%); 93% had not seen an anaesthetist at the time of the survey. Most believed anaesthesia involved 'going to sleep' (82%) and 71% expected to receive general anaesthesia. The preoperative anaesthesia visit was rated as important by 65% of patients. 78% indicated that provision of information would increase the likelihood of accepting regional anaesthesia. Reducing postoperative pain and nausea would influence 80% in choosing a regional technique. CONCLUSION: A knowledge deficit exists regarding anaesthesia modalities for upper limb trauma surgery.

An evaluation of operating room throughput in a stand-alone soft-tissue trauma operating theatre.

BACKGROUND: Operating room time is a limited, expensive commodity in acute hospitals. Strategies aimed at reduction of non-operative time improve operating room throughput and capacity. We conducted a prospective study to evaluate and augment operating room throughput and capacity using context-specific work practice changes. METHODS: Following institutional and ethical approval, an interdisciplinary group designed and introduced a series of work practice changes specific to a stand-alone soft tissue trauma theatre, comprising modifications to patient processing, staff behaviours and additional anaesthesiologist hours. Time intervals relating to each patient were measured during a 16 week period before and after implementing work practice changes. The primary outcome measure was non-operative time, with daily caseload and cancellations amongst secondary outcome measures. RESULTS: 251 procedures were included over 58 working days (8 to 17 Monday to Friday). Non-operative time [55.6 (31.1) vs 52.3 (9.8) minutes, p = 0.48], daily caseload [4 [1-9] vs 4 [2-7], p = 0.56], and the number of daily cancellations [3 [0-11] vs 5 [0-8], p = 0.38], did not differ between baseline and study phases. Regional anaesthesia for upper limb surgery increased during the study phase [26/59 (44.0%) vs 10/63 (15.9%), p = 0.014] with resultant decrease in mean duration of recovery room stay [20.7 (17.7) vs 30 (20.5) minutes, p = 0.0001] and increased recovery room bypass [26/116 (22.4%) vs 6/135 (4.4%), p = 0.0002]. Avoidable delays accounted for 124.8 (72.2) minutes of theatre time lost each day. CONCLUSION: In conclusion, additional attending anaesthesiologist hours combined with work practice changes did not impact on measures of theatre throughput and capacity. The study identified important variables that contribute to avoidable delays, and points the way for future research.

Diminished Quality of Life and Increased Brain Functional Connectivity in Patients with Hypothyroidism After Total Thyroidectomy.

BACKGROUND: Acute hypothyroidism induced by thyroid hormone withdrawal (THW) in patients with thyroid cancer after total thyroidectomy can affect mood and quality of life (QoL). While loss or dysregulation of thyroid hormone (TH) has these well-known behavioral consequences, the effects of TH alterations on brain function are not well understood. Resting state functional connectivity (FC) measured by functional magnetic resonance imaging (fMRI) allows non-invasive evaluation of human brain function. This study therefore examined whether THW affects resting state FC and whether changes in FC correlate with the mood or QoL of the patients with THW status. METHODS: Twenty-one patients who had undergone total thyroidectomy for thyroid cancer were recruited. Resting state fMRI scanning of the brain, thyroid function tests, and administration of the 12-Item Short Form Health Survey (SF-12) and the Patient Health Questionnaire-9 (PHQ-9) were performed before and after two weeks of THW. Regional homogeneity (ReHo), one of the measures of resting state FC, was calculated, and each voxel was compared between before and after THW in 19 patients. The ReHo values were extracted from the regions of interest showing within-group differences in ReHo values after THW, and correlations of ReHo values with thyrotropin (TSH) levels, total score of the PHQ-9, and composite scores of the SF-12 were statistically evaluated. RESULTS: Higher ReHo was observed after THW in the brain cortical regions across primary motor and sensory, visual, and association cortices. Among the regions, the ReHo values in the bilateral pre- and postcentral gyri, bilateral middle occipito-temporal cortices, the left precuneus, and the left lingual gyrus showed positive correlations with serum TSH levels after THW. Higher ReHo values in the bilateral pre- and postcentral gyri, the left middle temporo-occipital cortices, and the left ligual gyrus correlated with the lower mental component summary score from the SF-12, while higher ReHo values in the bilateral pre- and postcentral gyri correlated with higher total scores in the PHQ-9. CONCLUSIONS: Local brain FC is increased in the acute hypothyroid state. Higher FC correlates with a poorer mental QoL and increased depression in the hypothyroid state.

Resting-state EEG, impulsiveness, and personality in daily and nondaily smokers.

OBJECTIVES: Resting EEG is sensitive to transient, acute effects of nicotine administration and abstinence, but the chronic effects of smoking on EEG are poorly characterized. This study measures the resting EEG profile of chronic smokers in a non-deprived, non-peak state to test whether differences in smoking behavior and personality traits affect pharmaco-EEG response. METHODS: Resting EEG, impulsiveness, and personality measures were collected from daily smokers (n=22), nondaily smokers (n=31), and non-smokers (n=30). RESULTS: Daily smokers had reduced resting delta and alpha EEG power and higher impulsiveness (Barratt Impulsiveness Scale) compared to nondaily smokers and non-smokers. Both daily and nondaily smokers discounted delayed rewards more steeply, reported lower conscientiousness (NEO-FFI), and reported greater disinhibition and experience seeking (Sensation Seeking Scale) than non-smokers. Nondaily smokers reported greater sensory hedonia than nonsmokers. CONCLUSIONS: Altered resting EEG power in daily smokers demonstrates differences in neural signaling that correlated with greater smoking behavior and dependence. Although nondaily smokers share some characteristics with daily smokers that may predict smoking initiation and maintenance, they differ on measures of impulsiveness and resting EEG power. SIGNIFICANCE: Resting EEG in non-deprived chronic smokers provides a standard for comparison to peak and trough nicotine states and may serve as a biomarker for nicotine dependence, relapse risk, and recovery.

Time-Frequency Analysis of Peptide Microarray Data: Application to Brain Cancer Immunosignatures.

One of the gravest dangers facing cancer patients is an extended symptom-free lull between tumor initiation and the first diagnosis. Detection of tumors is critical for effective intervention. Using the body's immune system to detect and amplify tumor-specific signals may enable detection of cancer using an inexpensive immunoassay. Immunosignatures are one such assay: they provide a map of antibody interactions with random-sequence peptides. They enable detection of disease-specific patterns using classic train/test methods. However, to date, very little effort has gone into extracting information from the sequence of peptides that interact with disease-specific antibodies. Because it is difficult to represent all possible antigen peptides in a microarray format, we chose to synthesize only 330,000 peptides on a single immunosignature microarray. The 330,000 random-sequence peptides on the microarray represent 83% of all tetramers and 27% of all pentamers, creating an unbiased but substantial gap in the coverage of total sequence space. We therefore chose to examine many relatively short motifs from these random-sequence peptides. Time-variant analysis of recurrent subsequences provided a means to dissect amino acid sequences from the peptides while simultaneously retaining the antibody-peptide binding intensities. We first used a simple experiment in which monoclonal antibodies with known linear epitopes were exposed to these random-sequence peptides, and their binding intensities were used to create our algorithm. We then demonstrated the performance of the proposed algorithm by examining immunosignatures from patients with Glioblastoma multiformae (GBM), an aggressive form of brain cancer. Eight different frameshift targets were identified from the random-sequence peptides using this technique. If immune-reactive antigens can be identified using a relatively simple immune assay, it might enable a diagnostic test with sufficient sensitivity to detect tumors in a clinically useful way.

Neural correlates of performance monitoring in daily and intermittent smokers.

OBJECTIVES: Despite efforts that have increased smoking regulation, cigarette taxation, and social stigma, cigarette smoking remains the leading cause of preventable death worldwide, and a significant personal and public economic burden. In the U.S., intermittent smokers comprise approximately 22% of all smokers and represent a stable, non-dependent group that may possess protective factors that prevent the transition to dependence. One possibility is that intermittent smokers have intact CNS frontal regulatory and control mechanisms that enable resistance to nicotine-induced changes. METHODS: The present study measured inhibitory control using a flanker task and a go-nogo continuous performance tasks in daily dependent smokers, intermittent non-dependent smokers, and nonsmokers. Event-related potential (ERP) measures of were concurrently recorded to measure performance monitoring via Event-Related Negativity (ERN) and error positivity (Pe) components during error trials for each task. RESULTS: In both tasks, behavioral and ERN measures did not differ between groups; however, amplitude of the Pe component was largest among intermittent smokers. CONCLUSIONS: Thus, intermittent smokers differed from both daily smokers and nonsmokers on error processing, potentially revealing neuroprotective cognitive processes in nicotine dependence. SIGNIFICANCE: A better understanding of factors that mediate behavioral regulation may provide novel treatment approaches that help individuals achieve controlled smoking or cessation.

The effect of chronic cannabinoids on broadband EEG neural oscillations in humans.

Animal and cellular work has shown that central cannabinoid-1 receptors modulate neural oscillations in the gamma range (40 Hz), which may be important for normal perceptual and cognitive processes. In order to assess the effect of cannabinoids on broadband-frequency neural oscillations in humans, the current study examined the effect of chronic cannabis use on auditory steady-state responses (ASSRs) utilizing electroencephalography (EEG). Passive ASSRs were assessed using varying rates of binaural stimulation (auditory click-trains; 10-50 Hz in increments of 5 Hz; 80 dB SPL) in carefully screened cannabis users and controls. Chronic cannabis users (n=22; 12 h abstinence before study; positive 11-nor-9-carboxy-delta-9-tetrahydrocannabinol urine levels) and cannabis naïve controls (n=24) were evaluated. Time X frequency analyses on EEG data were performed using Fourier-based mean trial power (MTP) and phase-locking (inter-trial coherence; ITC). Transient ERPs to stimulus onset (auditory N100 components) were also evaluated. As predicted, a decrease in spectral power (MTP) at 40 Hz was observed in the cannabis group (p<0.018). No effects on phase-locking (ITC) or the N100 were observed. Further, within the cannabis group, lower 40 Hz power correlated with an earlier age of onset of cannabis use (p<0.04). These data suggest that chronic exposure to exogenous cannabinoids can alter the ability to generate neural oscillations, particularly in the gamma range. This is consistent with preclinical animal and cellular data, which may have implications for understanding the short- and long-term psychopharmacological effects of cannabis.

Analgesic efficacy of continuous femoral nerve block commenced prior to operative fixation of fractured neck of femur.

BACKGROUND: Peripheral nerve blocks are effective in treating acute pain, thereby minimizing the requirement for opiate analgesics. Fractured neck of femur (FNF) is a common, painful injury. The provision of effective analgesia to this cohort is challenging but an important determinant of their functional outcome. We investigated the analgesic efficacy of continuous femoral nerve block (CFNB) in patients with FNF. METHODS: Following institutional ethical approval and with informed consent, patients awaiting FNF surgery were randomly allocated to receive either standard opiate-based analgesia (Group 1) or a femoral perineural catheter (Group 2). Patients in Group 1 received parenteral morphine as required. Those in Group 2 received a CFNB comprising a bolus of local anaesthetic followed by a continuous infusion of 0.25% bupivacaine. For both Groups, rescue analgesia consisted of intramuscular morphine as required and all patients received paracetamol regularly. Pain was assessed using a visual analogue scale at rest and during passive movement (dynamic pain score) at 30 min following first analgesic intervention and six hourly thereafter for 72 hours. Patient satisfaction with the analgesic regimen received was recorded using verbal rating scores (0-10). The primary outcome measured was dynamic pain score from initial analgesic intervention to 72 hours later. RESULTS: Of 27 recruited, 24 patients successfully completed the study protocol and underwent per protocol analysis. The intervals from recruitment to the study until surgery were similar in both groups [31.4(17.7) vs 27.5(14.2) h, P = 0.57]. The groups were similar in terms of baseline clinical characteristics. For patients in Group 2, pain scores at rest were less than those reported by patients in Group 1 [9.5(9.4) vs 31(28), P = 0.031]. Dynamic pain scores reported by patients in Group 2 were less at each time point from 30 min up to 54 hours [e.g at 6 h 30.7(23.4) vs 67.0(32.0), P = 0.004]. Cumulative morphine consumption over 72 h was less in Group 2. Patient satisfaction scores were greater in Group 2 [9.4(1.1) vs 7.6(1.8), P = 0.014]. CONCLUSIONS: CFNB provides more effective perioperative analgesia than a standard opiate-based regimen for patients undergoing fixation of FNF. It is associated with lesser opiate use and greater patient satisfaction.

Proactive error analysis of ultrasound-guided axillary brachial plexus block performance.

BACKGROUND: Detailed description of the tasks anesthetists undertake during the performance of a complex procedure, such as ultrasound-guided peripheral nerve blockade, allows elements that are vulnerable to human error to be identified. We have applied 3 task analysis tools to one such procedure, namely, ultrasound-guided axillary brachial plexus blockade, with the intention that the results may form a basis to enhance training and performance of the procedure. METHODS: A hierarchical task analysis of the procedure was performed with subsequent analysis using systematic human error reduction and prediction approach (SHERPA). Failure modes, effects, and criticality analysis was applied to the output of our SHERPA analysis to provide a definitive hierarchy to the error analysis. RESULTS: Hierarchical task analysis identified 256 tasks associated with the performance of ultrasound-guided axillary brachial plexus blockade. Two hundred twelve proposed errors were analyzed using SHERPA. Failure modes, effects, and criticality analysis methodology was applied to the output of SHERPA analysis to prioritize 20 errors. CONCLUSIONS: This study presents a formal analysis of (i) the specific tasks that might be associated with the safe and effective performance of the procedure and (ii) the most critical errors likely to occur as trainees learn to perform the procedure. Potential applications of these data include curricular development and the design of tools to teach and assess block performance.

A longitudinal twin study of effects of adolescent alcohol abuse on the neurophysiology of attention and orienting.

BACKGROUND: Long-term functional brain effects of adolescent alcohol abuse remain uncertain, partially because of difficulties in distinguishing inherited deficits from neuronal effects of ethanol and by confounds associated with alcohol abuse, especially nicotine exposure. We conducted a longitudinal twin study to determine neurocognitive effects of adolescent alcohol abuse, as measured with the auditory event-related potential (ERP) component P3, a putative marker of genetic vulnerability to alcoholism. METHODS: Twin pairs (N=177; 150 selected for intrapair concordance/discordance for alcohol-related problems at age 18½) were recruited from ongoing studies of twins born 1975-1979 in Finland. Alcohol and tobacco use were assessed with questionnaires at ages 16, 17, 18½, and ~25, and by a structured psychiatric interview concurrent with the ERP testing at mean age 25.8. During ERP recordings, subjects were instructed to detect target tones within a train of frequent "standards" and to ignore occasional "novel" sounds. To distinguish familial factors from ethanol effects, ERP and self-reported alcohol use measures were incorporated into hierarchical multiple regression (HMR) analysis, and intrapair differences in ERP were associated with intra-pair differences in alcohol variables. RESULTS: Novel-sound P3 amplitude correlated negatively with self-reported alcohol use in both between- and within-family analyses. No similar effect was observed for target-tone P3. HMR results suggest that twins' similarity for novel-sound P3 amplitude is modulated by their alcohol use, and this effect of alcohol use is influenced by genetic factors. CONCLUSIONS: Our results, from a large sample of twins selected from a population-based registry for pairwise concordance/discordance for alcohol problems at 18½, demonstrate that adolescent alcohol abuse is associated with subtle neurophysiological changes in attention and orienting. The changes are reflected in decreased novel-sound P3 amplitude and may be modified by genetic factors.

Long versus short axis ultrasound guided approach for internal jugular vein cannulation: a prospective randomised controlled trial.

AIM: The aim of this study was to compare the short and long axis approaches to ultrasound guided right internal jugular vein cannulation with respect to indicators of success. METHODS: Patients undergoing cardiac surgery requiring central venous cannulation (99 patients) were randomised to undergo either long or short axis ultrasound guided cannulation of the right internal jugular vein by a skilled anaesthetist. First pass success, number of needle passes, procedural taken and complications were documented for each procedure. RESULTS: The right internal jugular vein was successfully cannulated in all 99 patients. The first pass success rate was significantly higher in the short axis 98% group compared to the long axis group 78% [48:1 (98%) versus 39:11 (78%) p <0.006]. Procedural time was comparable in both the groups [39.6 (18.4) versus 46.9 (42.4)]. Fewer needle redirections were required in the short axis group [1.02 (0.02) versus 1.24 (0.56) p <0.004]. Carotid artery puncture only occurred in the long axis group. CONCLUSIONS: We conclude that anaesthetists with experience in ultrasound guided internal jugular vein cannulation, have higher first pass success rate and less carotid artery puncture when a short axis, rather than a long axis, approach is employed.

Structural network topology revealed by white matter tractography in cannabis users: a graph theoretical analysis.

Endocannabinoid receptors modulate synaptic plasticity in the brain and may therefore impact cortical connectivity not only during development but also in response to substance abuse in later life. Such alterations may not be evident in volumetric measures utilized in brain imaging, but could affect the local and global organization of brain networks. To test this hypothesis, we used a novel computational approach to estimate network measures of structural brain connectivity derived from diffusion tensor imaging (DTI) and white matter tractography. Twelve adult cannabis (CB) users and 13 healthy subjects were evaluated using a graph theoretic analysis of both global and local brain network properties. Structural brain networks in both CB subjects and controls exhibited robust small-world network attributes in both groups. However, CB subjects showed significantly decreased global network efficiency and significantly increased clustering coefficients (degree to which nodes tend to cluster around individual nodes). CB subjects also exhibited altered patterns of local network organization in the cingulate region. Among all subjects, schizotypal and impulsive personality characteristics correlated with global efficiency but not with the clustering coefficient. Our data indicate that structural brain networks in CB subjects are less efficiently integrated and exhibit altered regional connectivity. These differences in network properties may reflect physiological processes secondary to substance abuse-induced synaptic plasticity, or differences in brain organization that increase vulnerability to substance use.

Auditory steady state response in bipolar disorder: relation to clinical state, cognitive performance, medication status, and substance disorders.

OBJECTIVES: Abnormalities in auditory steady state response (ASSR) at gamma range frequencies have been found in bipolar disorder, but the relationship of these neurophysiological disturbances to clinical factors has not been well characterized. We therefore evaluated the ASSR in bipolar disorder and examined its sensitivity to clinical symptoms, cognitive function, and pharmacological treatment. METHODS: A total of 68 patients with bipolar disorder and 77 control participants were evaluated. Click trains presented at 20, 30, 40, and 50 Hz evoked ASSRs. Mean trial power (MTP) and phase locking factor (PLF) measured response magnitude and phase synchronization of the ASSR at each stimulation frequency. Clinical state, pharmacological treatment, and neuropsychological performance were assessed, and their respective relationships with ASSR measures were evaluated. RESULTS: Patients with bipolar disorder showed reduced MTP and PLF compared to control participants. Bipolar disorder patients taking psychotropic medications had decreased PLF relative to patients withdrawn from medications. Control participants performed better on neuropsychological tests than bipolar disorder patients; however, test scores did not correlate with ASSR measures. CONCLUSIONS: Deficits in the generation and maintenance of ASSR are present in bipolar disorder, implicating disturbances in auditory pathways. ASSR may be sensitive to medication status. Other clinical features, including mood state, psychotic features, cognitive performance, smoking, or history of substance use disorder, were unrelated to MTP or PLF.