Electroconvulsive therapy for depression

An 82-year-old widowed woman with a history of recurrent unipolar major depression is referred to the electroconvulsive therapy (ECT) service of an academic medical center. During her illness, she has had four episodes of major depression consisting of periods of depressed mood, crying spells, loss of interest in usual activities, insomnia, loss of appetite and weight, difficulty with concentration, feelings of helplessness and hopelessness, and thoughts of suicide. During the current episode, which has lasted for 6 months, she has had typical symptoms of melancholic depression, as well as psychotic symptoms (e.g., a somatic delusion that she has terminal cancer), with suicidal ideation and a plan for taking a drug overdose. Previous treatment during this episode has included citalopram (Celexa), duloxetine (Cymbalta), and the combination of olanzepine (Zyprexa) and duloxetine, but the patient did not have a response to any of these agents. She could not tolerate the anticholinergic side effects of tricyclic antidepressants. Her psychiatrist seeks specialty consultation regarding the appropriateness and safety of ECT for this patient. THE CL INIC A L PROBL E M Major depressive disorder affects approximately 14 million adults in the United States each year. 1 The World Health Organization estimates that, at current rates, depression will be the second most common cause of disability worldwide by 2020. 2 Severe depression can impair the quality of life and lead to death by suicide; the lifetime risk of suicide among patients with affective disorders is 6 to 15%. Severe depression also increases the mortality associated with general medical conditions -most notably, heart disease. Depression in the elderly is a growing public health problem, with an estimated prevalence of 1 to 2% in the general population of elderly persons, 1 to 3% among those living in the community, and 10 to 12% among those in outpatient primary care and inpatient settings. 3 Major depression in older adults is a leading cause of disability, and it increases mortality from all causes and the likelihood of place ment in a nursing home. Although antidepressant medications are effective for many patients, the rate of response to the first agent administered can be as low as 50%. 5 The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial showed that the re mission rate decreased from 36.8% to 13.0% as successive treatment steps were required because of nonresponse. 6 Outcomes of treatment with antidepressant medications in the elderly may be suboptimal in part because of intolerance of side effects. Also, brain changes in depression in the elderly, especially abnormalities in frontostriatal limbic circuits, can attenuate the response to medications

Corticomotor Excitability during Observation and Imagination of a Work of Art

We examine the effects of the artistic representation – here exemplified by Michelangelo's Expulsion from Paradise – of an action on the motor system. Using single and paired- pulse transcranial magnetic stimulation we analyze corticomotor excitability during observation of an action in the painting, during imagery of the painting, and during observation of a photograph of the same pose. We also analyze the effects of observation of two further paintings, one showing the same muscles at rest, and in the other in a more overtly emotional context. Both observation of the Expulsion and of imagery of the painting increased cortical excitability. Neither the relaxed pose of Michelangelo's Creation nor the flexed posture in the highly emotional context of Bellini's Dead Christ increased cortical excitability. Observation of a photograph of the same extended pose did not increase cortical excitability either. Moreover, intracortical inhibition was reduced during imagery of the painting. Our results offer clear motor correlates of the relationship between the esthetic quality of a work and the perception of implied movement within it

Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive–compulsive disorder

In open trials, 1-Hz repetitive transcranial magnetic stimulation (rTMS) to the supplementary motor area (SMA) improved symptoms and normalized cortical hyper-excitability of patients with obsessive–compulsive disorder (OCD). Here we present the results of a randomized sham-controlled double-blind study. Medication-resistant OCD patients (n=21) were assigned 4 wk either active or sham rTMS to the SMA bilaterally. rTMS parameters consisted of 1200 pulses/d, at 1 Hz and 100% of motor threshold (MT). Eighteen patients completed the study. Response to treatment was defined as a ≽25% decrease on the Yale–Brown Obsessive Compulsive Scale (YBOCS). Non-responders to sham and responders to active or sham rTMS were offered four additional weeks of open active rTMS. After 4 wk, the response rate in the completer sample was 67% (6/9) with active and 22% (2/9) with sham rTMS. At 4 wk, patients receiving active rTMS showed on average a 25% reduction in the YBOCS compared to a 12% reduction in those receiving sham. In those who received 8-wk active rTMS, OCD symptoms improved from 28.2±5.8 to 14.5±3.6. In patients randomized to active rTMS, MT measures on the right hemisphere increased significantly over time. At the end of 4-wk rTMS the abnormal hemispheric laterality found in the group randomized to active rTMS normalized. The results of the first randomized sham-controlled trial of SMA stimulation in the treatment of resistant OCD support further investigation into the potential therapeutic applications of rTMS in this disabling condition

Applications of TMS to therapy in psychiatry

Summary: Transcranial magnetic stimulation (TMS) has been applied to a growing number of psychiatric disorders as a noninvasive probe to study the underlying neurobiologic processes involved in psychiatric disorders and as a putative treatment. Transcranial magnetic stimulation is unparalleled in its ability to test the hypotheses generated by functional neuroimaging studies by modulating activity in selected neural circuits. As a focal intervention that may in some cases exert lasting effects, TMS offers the hope of targeting and ameliorating the circuitry underlying psychiatric disorders. The ultimate success of such an approach depends on our knowledge of the neural circuitry underlying these disorders, of how TMS exerts its effects, and of how to control the application of TMS to exert the desired effects. Although most clinical trials have focused on the treatment of major depression, increasing attention has been paid to schizophrenia and anxiety disorders. Many of these trials have supported a significant effect of TMS, but in some studies the effect is small and short lived. Current challenges in the field include determining how to enhance the efficacy of TMS in these disorders and how to identify patients for whom TMS may be efficacious

Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive–compulsive disorder (OCD) and Tourette's syndrome (TS)

There is evidence that motor and premotor cortex are hyperexcitable in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). We tested whether low-frequency repetitive transcranial magnetic stimulation (rTMS) could normalize overactive motor cortical regions and thereby improve symptoms. Subjects with OCD or TS were treated with active rTMS to the supplementary motor area (SMA) for 10 daily sessions at 1 Hz, 100% of motor threshold, 1200 stimuli/day. Suggestions of clinical improvement were apparent as early as the first week of rTMS. At the second week of treatment, statistically significant reductions were seen in the YBOCS, YGTSS, CGI, HARS, HDRS, SAD, BDI, SCL-90, and SASS. Symptoms improvement was correlated with a significant increase of the right resting motor threshold and was stable at 3 months follow-up. Slow rTMS to SMA resulted in a significant clinical improvement and a normalization of the right hemisphere hyperexcitability, thereby restoring hemispheric symmetry in motor threshold

Using diffusion tensor imaging to identify corticospinal tract projection patterns in children with unilateral spastic cerebral palsy.

AIM: To determine whether diffusion tensor imaging (DTI) can be an independent assessment for identifying the corticospinal tract (CST) projecting from the more-affected motor cortex in children with unilateral spastic cerebral palsy (CP). METHOD: Twenty children with unilateral spastic CP participated in this study (16 males, four females; mean age 9y 2mo [standard deviation (SD) 3y 2mo], Manual Ability Classification System [MACS] level I-III). We used DTI tractography to reconstruct the CST projecting from the more-affected motor cortex. We mapped the motor representation of the more-affected hand by stimulating the more- and the less-affected motor cortex measured with single-pulse transcranial magnetic stimulation (TMS). We then verified the presence or absence of the contralateral CST by comparing the TMS map and DTI tractography. Fisher's exact test was used to determine the association between findings of TMS and DTI. RESULTS: DTI tractography successfully identified the CST controlling the more-affected hand (sensitivity=82%, specificity=78%). INTERPRETATION: Contralateral CST projecting from the lesioned motor cortex assessed by DTI is consistent with findings of TMS mapping. Since CST connectivity may be predictive of response to certain upper extremity treatments, DTI-identified CST connectivity may potentially be valuable for determining such connectivity where TMS is unavailable or inadvisable for children with seizures.K08 NS073796 - NINDS NIH HHS; TL1 RR024158 - NCRR NIH HHS; K01 NS062116 - NINDS NIH HHS; UL1 RR024156 - NCRR NIH HHS; KL2 RR024157 - NCRR NIH HHS; R01 HD076436 - NICHD NIH HHSPublished versio

Extended Remediation of Sleep Deprived-Induced Working Memory Deficits Using fMRI-Guided Transcranial Magnetic Stimulation

STUDY OBJECTIVES: We attempted to prevent the development of working memory (WM) impairments caused by sleep deprivation using fMRI-guided repetitive transcranial magnetic stimulation (rTMS). Novel aspects of our fMRI-guided rTMS paradigm included the use of sophisticated covariance methods to identify functional networks in imaging data, and the use of fMRI-targeted rTMS concurrent with task performance to modulate plasticity effects over a longer term. DESIGN: Between-groups mixed model. SETTING: TMS, MRI, and sleep laboratory study. PARTICIPANTS: 27 subjects (13 receiving Active rTMS, and 14 Sham) completed the sleep deprivation protocol, with another 21 (10 Active, 11 Sham) non-sleep deprived subjects run in a second experiment. INTERVENTIONS: Our previous covariance analysis had identified a network, including occipital cortex, which demonstrated individual differences in resilience to the deleterious effects of sleep deprivation on WM performance. Five Hz rTMS was applied to left lateral occipital cortex while subjects performed a WM task during 4 sessions over the course of 2 days of total sleep deprivation. MEASUREMENTS AND RESULTS: At the end of the sleep deprivation period, Sham sleep deprived subjects exhibited degraded performance in the WM task. In contrast, those receiving Active rTMS did not show the slowing and lapsing typical in sleep deprivation, and instead performed similarly to non- sleep deprived subjects. Importantly, the Active sleep deprivation group showed rTMS-induced facilitation of WM performance a full 18 hours after the last rTMS session. CONCLUSIONS: Over the course of sleep deprivation, these results indicate that rTMS applied concurrently with WM task performance affected neural circuitry involved in WM to prevent its full impact

Regional Cerebral Blood Flow and Metabolic Rate in Persistent Lyme Encephalopathy

Context: There is controversy regarding whether objective neurobiological abnormalities exist after intensive antibiotic treatment for Lyme disease. Objectives: To determine whether patients with a history of well-characterized Lyme disease and persistent cognitive deficit show abnormalities in global or topographic distributions of regional cerebral blood flow (rCBF) or cerebral metabolic rate (rCMR). Design: Case-controlled study. Setting: A university medical center. Participants: A total of 35 patients and 17 healthy volunteers (controls). Patients had well-documented prior Lyme disease, a currently reactive IgG Western blot, prior treatment with at least 3 weeks of intravenous cephalosporin, and objective memory impairment. Main Outcome Measures: Patients with persistent Lyme encephalopathy were compared with age-, sex-, and education-matched controls. Fully quantified assessments of rCBF and rCMR for glucose were obtained while subjects were medication-free using positron emission tomography. The CBF was assessed in 2 resting room air conditions (without snorkel and with snorkel) and 1 challenge condition (room air enhanced with carbon dioxide, ie, hypercapnia). Results: Statistical parametric mapping analyses revealed regional abnormalities in all rCBF and rCMR measurements that were consistent in location across imaging methods and primarily reflected hypoactivity. Deficits were noted in bilateral gray and white matter regions, primarily in the temporal, parietal, and limbic areas. Although diminished global hypercapnic CBF reactivity (P < .02) was suggestive of a component of vascular compromise, the close coupling between CBF and CMR suggests that the regional abnormalities are primarily metabolically driven. Patients did not differ from controls on global resting CBF and CMR measurements. Conclusions: Patients with persistent Lyme encephalopathy have objectively quantifiable topographic abnormalities in functional brain activity. These CBF and CMR reductions were observed in all measurement conditions. Future research should address whether this pattern is also seen in acute neurologic Lyme disease

Training in the practice of noninvasive brain stimulation: Recommendations from an IFCN committee

© 2020 As the field of noninvasive brain stimulation (NIBS) expands, there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three different types of practitioners are considered (Technicians, Clinicians, and Scientists), to attempt to cover the range of education and responsibilities of practitioners in NIBS from the laboratory to the clinic. Basic or core competencies and more advanced knowledge and skills are discussed, and recommendations offered regarding didactic and practical curricular components. We encourage individual licensing and governing bodies to implement these guidelines