Mahendra T. Bhati, M.D.

All Publications

• Naturalistic Clinical Monitoring of rTMS-Induced Plasticity With TMS-EEG Keller, C., Wu, W., Sarhadi, K., Zhang, Y., Kerwin, L., Bhati, M., Etkin, A. ELSEVIER SCIENCE INC. 2018: S195

  View details for Web of Science ID 000432466300487

• Deep Brain Stimulation for Alzheimer's Disease: Ethical Challenges for Clinical Research. Journal of Alzheimer's disease : JAD Siegel, A. M., Barrett, M. S., Bhati, M. T. 2017; 56 (2): 429-439

  Abstract

  Deep brain stimulation (DBS) is an invasive neuromodulation modality that has shown early promise as a novel treatment of Alzheimer's disease (AD). Further clinical research is warranted on the basis of positive results from animal and human studies, as well as the inadequacy of existing treatments in reducing the enormous medical and financial costs of untreated AD. Nevertheless, unique ethical challenges require particular attention to elements of subject enrollment and informed consent. Study protocols should specify robust assessment and regular monitoring of subject decision-making capacity to consent to trial participation. Investigators should also assess for and mitigate therapeutic misconception (the phenomenon whereby a research participant conflates the goals of research with those of clinical treatment) and ensure that all prospective trial participants have adequate post-trial access to treatment and DBS device maintenance. In the following discussion, each issue is summarized and followed by recommendations for proper ethical procedure. We conclude by assimilating relevant ethical considerations into a decision-making algorithm designed to aid future clinical investigators of DBS for AD with the task of ethical subject enrollment.

  View details for DOI 10.3233/JAD-160356

  View details for PubMedID 27983548

• Deciphering deep brain stimulation for depression. The lancet. Psychiatry Bhati, M. T., Halpern, C. H. 2017

  View details for DOI 10.1016/S2215-0366(17)30396-6

  View details for PubMedID 28988905

• A naturalistic, multi-site study of repetitive transcranial magnetic stimulation therapy for depression. Journal of affective disorders Taylor, S. F., Bhati, M. T., Dubin, M. J., Hawkins, J. M., Lisanby, S. H., Morales, O., Reti, I. M., Sampson, S., Short, E. B., Spino, C., Watcharotone, K., Wright, J. 2016; 208: 284–90

  Abstract

  Repetitive transcranial magnetic stimulation (rTMS) was approved in 2008 in the United States, and there are relatively few studies describing its use in regular clinical practice since approval.From April 2011 to October 2014, ten sites within the National Network of Depression Centers (NNDC) provided data on 62 evaluable patients with a depressive episode. Treatment was determined naturalistically. Response was assessed by the Quick Inventory of Depressive Symptoms, Self-Report (QIDS-SR) as the primary outcome, and the Patient Health Questionnaire-9 (PHQ-9) and the clinician-rated Clinical Global Impression (CGI) as secondary depression measures.Enrolled patients exhibited significant treatment resistance, with 70.2% reporting more than 4 prior depressive episodes. Most patients received treatment with standard parameters (10Hz over the left dorsolateral prefrontal cortex), although 22.6% of the patients received 1 or 5Hz stimulation at some point. Over 6 weeks of treatment, response and remission rates were 29.4% and 5.9%, respectively, for the QIDS-SR; 39.2% and 15.7%, respectively, for the PHQ-9; and 50.9% and 17.9%, respectively, for the CGI. Moderator analyses revealed no effect of prior depressive episodes, history of ECT or gender, although early life stress predicted a better response to rTMS therapy.The study was an open-label, registry trial, with relatively coarse clinical data, reflecting practice only in academic, depression-specialty centers. Because of the relatively small size and heterogeneity of the sample, type 2 errors are possible and positive findings are in need of replication.rTMS demonstrates effectiveness in clinical practice within the NNDC, although remission rates appear slightly lower in comparison with other recent naturalistic studies.

  View details for DOI 10.1016/j.jad.2016.08.049

  View details for PubMedID 27794252

• A Commentary on Attitudes Towards Deep Brain Stimulation for Addiction. Journal of neurology & neuromedicine Lee, K. E., Bhati, M. T., Halpern, C. H. 2016; 1 (8): 1–3

  Abstract

  Deep brain stimulation (DBS) has proven to be an effective treatment for neurologic disorders such as Parkinson's disease, and is currently being investigated as a therapy for psychiatric diseases such as addiction, major depressive disorder, and obsessive compulsive disorder. In this commentary, we review and discuss the findings presented in the Letter to the Editor entitled "Attitudes towards treating addiction with deep brain stimulation," written by Ali et al(1). The survey presented in this Letter reported general approval for examining the effects of DBS on addictive disorders in a clinical trial, but highlighted critical areas of concern including informed consent, patient autonomy, appropriate medical practice, passing of clinical trial milestones, and implications on law enforcement.

  View details for PubMedID 28620655

• Cognitive outcome after ventral capsule/ventral striatum stimulation for treatment-resistant major depression. Journal of neurology, neurosurgery, and psychiatry Kubu, C. S., Brelje, T., Butters, M. A., Deckersbach, T., Malloy, P., Moberg, P., Tröster, A. I., Williamson, E., Baltuch, G. H., Bhati, M. T., Carpenter, L. L., Dougherty, D. D., Howland, R. H., Rezai, A. R., Malone, D. A. 2016

  Abstract

  We report the neuropsychological outcome of 25 patients with treatment-resistant major depressive disorder (TRD) who participated in an Institutional Review Board (IRB)-approved randomised double-blind trial comparing active to sham deep brain stimulation (DBS) in the anterior limb of the ventral capsule/ventral striatum (VC/VS).Participants were randomised to active (n=12) versus sham (n=13) DBS for 16 weeks. Data were analysed at the individual and group levels. Group differences were analysed using repeated measures ANOVAs. Relationships between depression severity and cognition were examined using partial correlations. The false discovery rate method controlled for multiple analyses.No significant interactions comparing active versus sham stimulation over time were evident. Change in depression was unrelated to change in neuropsychological measures. Twenty patients declined by ≥1 SD on at least one measure (41.3% of declines occurred in active group participants; 63.0% in older participants regardless of stimulation status). Twenty-two patients exhibited improvements >1 SD on neuropsychological measures (47.7% in the active group; 63.1% in younger participants).These data suggest that VC/VS DBS in patients with TRD does not significantly affect neuropsychological function. Age at surgery, regardless of stimulation status, may be related to cognitive outcome at the individual patient level.NCT00837486; Results.

  View details for DOI 10.1136/jnnp-2016-313803

  View details for PubMedID 27659923

• A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression BIOLOGICAL PSYCHIATRY Dougherty, D. D., Rezai, A. R., Carpenter, L. L., Howland, R. H., Bhati, M. T., O'Reardon, J. P., Eskandar, E. N., Baltuch, G. H., Machado, A. D., Kondziolka, D., Cusin, C., Evans, K. C., Price, L. H., Jacobs, K., Pandya, M., Denko, T., Tyrka, A. R., Brelje, T., Deckersbach, T., Kubu, C., Malone, D. A. 2015; 78 (4): 240-248

  Abstract

  Multiple open-label trials of deep brain stimulation (DBS) for treatment-resistant depression (TRD), including those targeting the ventral capsule/ventral striatum target, have shown encouraging response rates. However, no randomized controlled trials of DBS for TRD have been published.Thirty patients with TRD participated in a sham-controlled trial of DBS at the ventral capsule/ventral striatum target for TRD. Patients were randomized to active versus sham DBS treatment in a blinded fashion for 16 weeks, followed by an open-label continuation phase. The primary outcome measure was response, defined as a 50% or greater improvement on the Montgomery-Åsberg Depression Rating Scale from baseline.There was no significant difference in response rates between the active (3 of 15 subjects; 20%) and control (2 of 14 subjects; 14.3%) treatment arms and no significant difference between change in Montgomery-Åsberg Depression Rating Scale scores as a continuous measure upon completion of the 16-week controlled phase of the trial. The response rates at 12, 18, and 24 months during the open-label continuation phase were 20%, 26.7%, and 23.3%, respectively.The results of this first randomized controlled study of DBS for the treatment of TRD did not demonstrate a significant difference in response rates between the active and control groups at the end of the 16-week controlled phase. However, a range of 20% to 26.7% of patients did achieve response at any time during the open-label continuation phase. Future studies, perhaps utilizing alternative study designs and stimulation parameters, are needed.

  View details for DOI 10.1016/j.biopsych.2014.11.023

  View details for Web of Science ID 000358084200010

  View details for PubMedID 25726497

• Efficacy and Safety of Low-field Synchronized Transcranial Magnetic Stimulation (sTMS) for Treatment of Major Depression BRAIN STIMULATION Leuchter, A. F., Cook, I. A., Feifel, D., Goethe, J. W., Husain, M., Carpenter, L. L., Thase, M. E., Krystal, A. D., Philip, N. S., Bhati, M. T., Burke, W. J., Howland, R. H., Sheline, Y. I., Aaronson, S. T., Iosifescu, D. V., O'Reardon, J. P., Gilmer, W. S., Jain, R., Burgoyne, K. S., Phillips, B., Manberg, P. J., Massaro, J., Hunter, A. M., Lisanby, S. H., George, M. S. 2015; 8 (4): 787-794

  Abstract

  Transcranial Magnetic Stimulation (TMS) customarily uses high-field electromagnets to achieve therapeutic efficacy in Major Depressive Disorder (MDD). Low-field magnetic stimulation also may be useful for treatment of MDD, with fewer treatment-emergent adverse events.To examine efficacy, safety, and tolerability of low-field magnetic stimulation synchronized to an individual's alpha frequency (IAF) (synchronized TMS, or sTMS) for treatment of MDD.Six-week double-blind sham-controlled treatment trial of a novel device that used three rotating neodymium magnets to deliver sTMS treatment. IAF was determined from a single-channel EEG prior to first treatment. Subjects had baseline 17-item Hamilton Depression Rating Scale (HamD17) ≥ 17.202 subjects comprised the intent-to-treat (ITT) sample, and 120 subjects completed treatment per-protocol (PP). There was no difference in efficacy between active and sham in the ITT sample. Subjects in the PP sample (N = 59), however, had significantly greater mean decrease in HamD17 than sham (N = 60) (-9.00 vs. -6.56, P = 0.033). PP subjects with a history of poor response or intolerance to medication showed greater improvement with sTMS than did treatment-naïve subjects (-8.58 vs. -4.25, P = 0.017). Efficacy in the PP sample reflects exclusion of subjects who received fewer than 80% of scheduled treatments or were inadvertently treated at the incorrect IAF; these subgroups failed to separate from sham. There was no difference in adverse events between sTMS and sham, and no serious adverse events attributable to sTMS.Results suggest that sTMS may be effective, safe, and well tolerated for treating MDD when administered as intended.

  View details for DOI 10.1016/j.brs.2015.05.005

  View details for Web of Science ID 000357542100014

  View details for PubMedID 26143022

• Defining Psychosis: The Evolution of DSM-5 Schizophrenia Spectrum Disorders CURRENT PSYCHIATRY REPORTS Bhati, M. T. 2013; 15 (11)

  Abstract

  Descriptions of mental illness exist throughout recorded history. However, until the mid-twentieth century, there was no standard nosology or diagnostic standard for mental disorders. This limited understanding of these disorders and development of better treatments. As conditions such as dementia praecox and schizophrenia were being described, collaborative efforts were made in the twentieth century to develop the first Diagnostic and Statistical Manual of Mental Disorders (DSM). This review provides an overview of the history of psychiatric diagnosis with a focus on the history of schizophrenia as a diagnosis in the DSM. DSM-5 updates to diagnostic criteria for schizophrenia and related disorders are provided. Limitations to diagnostic validity and reliability are discussed in addition to changes in diagnostic approaches to schizophrenia spectrum and other psychotic disorders in an effort to improve diagnostic validity and reliability. The DSM-5 reflects the culmination of an ongoing collaborative effort to improve the diagnosis of mental disorders, and future research in Research Domain Criteria (RDoC) will help provide convergent validity when understanding and treating mental illnesses.

  View details for DOI 10.1007/s11920-013-0409-9

  View details for Web of Science ID 000326187300006

  View details for PubMedID 24057160

• Effect of retrieval effort and switching demand on fMRI activation during semantic word generation in schizophrenia SCHIZOPHRENIA RESEARCH Ragland, J. D., Moelter, S. T., Bhati, M. T., Valdez, J. N., Kohlerc, C. G., Siegel, S. J., Gur, R. C., Gur, R. E. 2008; 99 (1-3): 312-323

  Abstract

  Verbal fluency deficits in schizophrenia are difficult to interpret because the tasks are multi-factorial and groups differ in total words generated. We manipulated retrieval and switching demands by requiring alternation between over-learned sequences in which retrieval is relatively automatic (OS) and semantic categories requiring increased retrieval effort (SC). Controlled processing was also manipulated by including switching and non-switching conditions, and formal thought disorder (FTD) was assessed with the communication disorders index (CDI). The OS/SC semantic fluency paradigm was administered during fMRI to 13 patients with schizophrenia and 14 matched controls. Images were acquired on a 3 Tesla Siemens scanner using compressed image acquisition to allow for cued overt word production. Subjects alternated between OS, SC, OS-switch, SC-switch, and baseline blocks. Images were pre-processed in SPM-2, and a two-stage random effects analysis tested within and between group contrasts. There were no group performance differences. fMRI analysis did not reveal any group differences during the OS non-switching condition. Both groups produced expected activation in bilateral prefrontal and inferior parietal regions. However, during the SC condition patients had greater activation than controls in left prefrontal, right anterior cingulate, right superior temporal, bilateral thalamus, and left parietal regions. There was also evidence of patient over-activation in prefrontal, superior temporal, superior parietal, and visual association areas when a switching component was added. FTD was negatively correlated with BOLD response in the right anterior cingulate, cuneus and superior frontal gyrus during increased retrieval demand, and positively correlated with fMRI activation in the left lingual gyrus, right fusiform gyrus and left superior parietal lobule during increased switching demand. These results indicate that patients are able to successfully perform effortful semantic fluency tasks during non-speeded conditions. When retrieval is relatively automatic there does not appear to be an effect of schizophrenia on fMRI response. However, when retrieval and controlled processing demands increase, patients have greater activation than controls despite unimpaired task performance. This inefficient BOLD response may explain why patients are slower and less accurate on standard self-paced fluency tasks.

  View details for Web of Science ID 000254306600037

  View details for PubMedID 18155880

• Facial emotion recognition in schizophrenia: When and why does it go awry? SCHIZOPHRENIA RESEARCH Turetsky, B. I., Kohler, C. G., Indersmitten, T., Bhati, M. T., Charbonnier, D., Gur, R. C. 2007; 94 (1-3): 253-263

  Abstract

  Schizophrenia patients demonstrate impaired emotional processing that may be due, in part, to impaired facial emotion recognition. This study examined event-related potential (ERP) responses to emotional faces in schizophrenia patients and controls to determine when, in the temporal processing stream, patient abnormalities occur.16 patients and 16 healthy control participants performed a facial emotion recognition task. Very sad, somewhat sad, neutral, somewhat happy, and very happy faces were each presented for 100 ms. Subjects indicated whether each face was "Happy", "Neutral", or "Sad". Evoked potential data were obtained using a 32-channel EEG system.Controls performed better than patients in recognizing facial emotions. In patients, better recognition of happy faces correlated with less severe negative symptoms. Four ERP components corresponding to the P100, N170, N250, and P300 were identified. Group differences were noted for the N170 "face processing" component that underlies the structural encoding of facial features, but not for the subsequent N250 "affect modulation" component. Higher amplitude of the N170 response to sad faces was correlated with less severe delusional symptoms. Although P300 abnormalities were found, the variance of this component was explained by the earlier N170 response.Patients with schizophrenia demonstrate abnormalities in early visual encoding of facial features that precedes the ERP response typically associated with facial affect recognition. This suggests that affect recognition deficits, at least for happy and sad discrimination, are secondary to faulty structural encoding of faces. The association of abnormal face encoding with delusions may denote the physiological basis for clinical misidentification syndromes.

  View details for DOI 10.1016/j.schres.2007.05.001

  View details for Web of Science ID 000248638500032

  View details for PubMedID 17583481

• Clinical manifestations, diagnosis, and empirical treatments for catatonia. Psychiatry (Edgmont (Pa. : Township)) Bhati, M. T., Datto, C. J., O'Reardon, J. P. 2007; 4 (3): 46-52

  Abstract

  Review the medical literature on the history and clinical features of catatonia so as to provide a contemporary clinical guide for successfully diagnosing and treating the various clinical forms of catatonia.RESULTS of MEDLINE computerized searches using search terms 'catatonia', 'treatment of catatonia', 'electroconvulsive therapy and catatonia', 'benzodiazepines and catatonia', clinical case reports, and book chapters covering the medical and psychiatric literature relevant to catatonia and its associated treatments were examined.Academic medical center.None.None.Catatonia is a common but under-recognized clinical syndrome. No large-scale, controlled studies exist to determine the relative effectiveness of current treatments, including sedative-hypnotic medications (benzodiazepines or barbiturates), and electroconvulsive therapy (ECT).Despite the lack of large-scale, controlled studies, benzodiazepines appear to be an effective first-line treatment for catatonia. ECT is now often reserved as a second-line treatment despite more than 60 years of documented efficacy and safety. However, ECT should be viewed as a first-line intervention in cases of severe or malignant catatonias.

  View details for PubMedID 20805910

• Catatonia and prediction of response to ECT Psychiatric Annals Caroff, S. N., Ungvari, G. S., Bhati, M. T., Datto, C. J., O'Reardon, J. P. 2007; 32 (1): 57-64
• The brain, language, and schizophrenia. Current psychiatry reports Bhati, M. T. 2005; 7 (4): 297-303

  Abstract

  Language is a defining and prominent feature in humans. This faculty is impaired in those with schizophrenia. Individuals with schizophrenia show numerous abnormalities in language function, including symptoms of disorganized speech, auditory hallucinations, thought disorders, and verbal memory impairments. Structural and functional brain imaging with neurocognitive testing shows various aspects of brain structure and function associated with language that also are abnormal in schizophrenia. This article comparatively reviews this research and relates it to understanding the symptoms and pathophysiologic features of schizophrenia. Understanding the neural basis of language and its disruption in schizophrenia provides a guide for diagnosis, subtyping, treatment, and future research.

  View details for PubMedID 16098284

• What makes aripiprazole the ‘different’ antipsychotic. Current Psychiatry Bhati, M. T. 2005; 4 (7): 51-60