Sally E. Herring

A Randomized Trial of rTMS Targeted with MRI Based Neuro-Navigation in Treatment-Resistant Depression

The aim of this study is to investigate whether repetitive transcranial magnetic stimulation (rTMS) targeted to a specific site in the dorsolateral prefrontal cortex (DLPFC), with a neuro-navigational method based on structural MRI, would be more effective than rTMS applied using the standard localization technique. Fifty-one patients with treatment-resistant depression were randomized to receive a 3-week course (with a potential 1-week extension) of high-frequency (10 Hz) left-sided rTMS. Thirty trains (5 s duration) were applied daily 5 days per week at 100% of the resting motor threshold. Treatment was targeted with either the standard 5 cm technique (n=27) or using a neuro-navigational approach (n=24). This involved localizing the scalp location that corresponds to a specific site at the junction of Brodmann areas 46 and 9 in the DLPFC based on each individual subjects MRI scan. There was an overall significant reduction in the Montgomery–Asberg Depression Rating Scale scores over the course of the trial, and a better outcome in the targeted group compared with the standard localization group at 4 weeks (p=0.02). Significant differences were also found on secondary outcome variables. The use of neuro-navigational methods to target a specific DLPFC site appears to enhance response to rTMS treatment in depression. Further research is required to confirm this in larger samples, or to establish whether an alternate method based on surface anatomy, including measurement from motor cortex, can be substituted for the standard 5 cm method.

Mirror neuron activation is associated with facial emotion processing.

Theoretical accounts suggest that mirror neurons play a crucial role in social cognition. The current study used transcranial magnetic stimulation (TMS) to investigate the association between mirror neuron activation and facial emotion processing, a fundamental aspect of social cognition, among healthy adults (n=20). Facial emotion processing of static (but not dynamic) images correlated significantly with an enhanced motor response, proposed to reflect mirror neuron activation. These correlations did not appear to reflect general facial processing or pattern recognition, and provide support to current theoretical accounts linking the mirror neuron system to aspects of social cognition. We discuss the mechanism by which mirror neurons might facilitate facial emotion recognition.

Reduced motor facilitation during action observation in schizophrenia: A mirror neuron deficit?

Impairments in social cognitive functioning are well documented in schizophrenia, however the neural basis of these deficits is unclear. A recent explanatory model of social cognition centers upon the activity of mirror neurons, which are cortical brain cells that become active during both the performance and observation of behavior. Here, we test for the first time whether mirror neuron functioning is reduced in schizophrenia. Fifteen individuals with schizophrenia or schizoaffective disorder and fifteen healthy controls completed a transcranial magnetic stimulation (TMS) experiment designed to assess mirror neuron activation. While patients demonstrated no abnormalities in cortical excitability, motor facilitation during action observation, putatively reflecting mirror neuron activity, was reduced in schizophrenia. Dysfunction within the mirror neuron system may contribute to the pathophysiology of schizophrenia.

A double blind randomized trial of unilateral left and bilateral prefrontal cortex transcranial magnetic stimulation in treatment resistant major depression

OBJECTIVE A substantive body of research has demonstrated the efficacy of repetitive transcranial magnetic stimulation treatment (rTMS) in patients with depression. However, the parameters needed to optimize therapeutic efficacy remain unclear. The aim of this study was to investigate whether there is an advantage in efficacy of sequential bilateral rTMS compared to standard high-frequency left sided rTMS. METHOD Sixty seven patients with treatment resistant depression were included in a randomised double-blind sham controlled trial of sequential bilateral rTMS compared to standard high-frequency left sided rTMS and sham rTMS over a three-week period. The study also included a further three week comparison of the two active treatment conditions. The primary outcome variable was scores on the 17-item Hamilton Depression Rating Scale (HAMD). RESULTS In the three-week double-blind phase of the trial there was a greater antidepressant response to unilateral left sided rTMS compared with sham or bilateral rTMS. Across the full six weeks of active rTMS, there was also a consistent pattern of improved response in unilateral left compared to bilateral treatment. Response rates were low in both active groups. CONCLUSIONS This study does not support the hypothesis that sequential bilateral rTMS is more effective than unilateral high-frequency left-sided rTMS.

A study of the effectiveness of bilateral transcranial magnetic stimulation in the treatment of the negative symptoms of schizophrenia

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is increasingly being investigated as a potential treatment for a number of psychiatric disorders, including schizophrenia. Previous rTMS studies have targeted the left-side prefrontal cortex (PFC) in the treatment of negative symptoms, with inconsistent findings. Some imaging evidence suggests right-sided or bilateral PFC involvement in negative symptoms, areas yet to be investigated for rTMS treatment. The study therefore aimed to assess the efficacy of bilateral high-frequency rTMS in the treatment of negative symptoms. METHODS A 2-arm double-blind randomized controlled trial was conducted with 20 patients with a diagnosis of schizophrenia or schizoaffective disorder, and moderate-to-severe treatment-resistant negative symptoms. Participants received a 3-week course of high-frequency bilateral rTMS or sham. Twenty trains (5 seconds duration) of 10 Hz rTMS at 110% of the RMT were administered to each PFC daily, 5 days a week. RESULTS No significant group or time differences in the Scale for the Assessment of Negative Symptoms (SANS) scores or cognitive outcomes were evident. However, a trend for greater reduction in scores on the autistic preoccupation scale of the Positive and Negative Symptom Scale for the active group compared to the sham group was observed (P = .05). CONCLUSIONS No substantial benefit of high-frequency bilateral rTMS was seen in the treatment of the negative symptoms of schizophrenia. Further research is required to explore whether rTMS may have benefits specific to particular cognitive or symptom domains.

Symptom Correlates of Static and Dynamic Facial Affect Processing in Schizophrenia: Evidence of a Double Dissociation?

Schizophrenia patients have been shown to be compromised in their ability to recognize facial emotion. This deficit has been shown to be related to negative symptoms severity. However, to date, most studies have used static rather than dynamic depictions of faces. Nineteen patients with schizophrenia were compared with seventeen controls on 2 tasks; the first involving the discrimination of facial identity, emotion, and butterfly wings; the second testing emotion recognition using both static and dynamic stimuli. In the first task, the patients performed more poorly than controls for emotion discrimination only, confirming a specific deficit in facial emotion recognition. In the second task, patients performed more poorly in both static and dynamic facial emotion processing. An interesting pattern of associations suggestive of a possible double dissociation emerged in relation to correlations with symptom ratings: high negative symptom ratings were associated with poorer recognition of static displays of emotion, whereas high positive symptom ratings were associated with poorer recognition of dynamic displays of emotion. However, while the strength of associations between negative symptom ratings and accuracy during static and dynamic facial emotion processing was significantly different, those between positive symptom ratings and task performance were not. The results confirm a facial emotion-processing deficit in schizophrenia using more ecologically valid dynamic expressions of emotion. The pattern of findings may reflect differential patterns of cortical dysfunction associated with negative and positive symptoms of schizophrenia in the context of differential neural mechanisms for the processing of static and dynamic displays of facial emotion.

PILOT STUDY OF THE CLINICAL AND COGNITIVE EFFECTS OF HIGH‐FREQUENCY MAGNETIC SEIZURE THERAPY IN MAJOR DEPRESSIVE DISORDER

Electroconvulsive therapy (ECT) is a very commonly used treatment for patients with severe and treatment‐resistant depression. Although effective, this treatment is complicated by a number of side effects including cognitive impairment motivating attempts to develop treatment alternatives. Magnetic seizure therapy (MST) is a brain stimulation technique using a high‐powered transcranial magnetic stimulation device to produce therapeutic seizures. Preliminary research suggests that MST has antidepressant activity in the absence of cognitive side effects. The aim of this study was therefore to investigate the therapeutic efficacy and cognitive profile of MST provided at high frequency (100 Hz) and potentially longer stimulation trains and longer treatment courses than have been previously investigated.

A study of the effectiveness of high-frequency left prefrontal cortex transcranial magnetic stimulation in major depression in patients who have not responded to right-sided stimulation

The objective of this study was to explore the response rate to high-frequency left-sided repetitive transcranial magnetic stimulation (rTMS) in patients who had failed to respond to right-sided low-frequency stimulation, and to investigate whether there was differential efficacy between stimulation at 5 or 10 Hz. Data from two randomized controlled trials were pooled. In both studies a group of patients were randomized to receive either 5- or 10-Hz left prefrontal rTMS after failing to respond to right-sided stimulation. These patients received blinded 5- or 10-Hz stimulation (but without a sham control) for a period of up to 4 weeks and outcomes were compared. There was a small but significant overall response to left-sided rTMS but no difference in response between the 5- and 10-Hz treatment conditions. There appears to be a significant but modest likelihood of response to left-sided TMS in patients who fail right-sided stimulation, but there is no difference in efficacy between 5- and 10-Hz stimulation.

Transcranial magnetic stimulation for depression after a traumatic brain injury: a case study.

Depression after a traumatic brain injury (TBI) is very common, yet there is a lack of evidence-based treatment options for people who experience depression after a TBI. Traditionally, a history of TBI has been considered an exclusion criterion for transcranial magnetic stimulation trials because of the increased risk of seizure after a TBI. We present what we believe to be the first case of a patient with depression after a TBI treated with transcranial magnetic stimulation.

A pilot study of bed nucleus of the stria terminalis deep brain stimulation in treatment-resistant depression.

BACKGROUND Studies are increasingly investigating the therapeutic effects of deep brain stimulation (DBS) applied to a variety of brain regions in the treatment of patients with highly treatment refractory depression. Limited research to date has investigated the therapeutic potential of DBS applied to the Bed Nucleus Of Stria Terminalis (BNST). OBJECTIVE The aim of this study was to explore the therapeutic potential of DBS applied to the BNST. METHOD Five patients with highly treatment resistant depression underwent DBS to the BNST in an open label case series design. RESULTS BNST DBS resulted in sustained remission of depression in two of the five patients, provided substantial therapeutic improvement two further patients, and had minimal antidepressant effect for the final patient. There were no operative complications and stimulation related side effects were limited and reversible with adjustment of stimulation. However, the time to achieve and complexity of programming required to achieve optimal therapeutic outcomes varied substantially between patients. CONCLUSION DBS applied to the BNST as therapeutic potential in patients with highly refractory depression and warrants exploration in larger clinical studies.