Richard H. Thomson

The effect of test TMS intensity on short-interval intracortical inhibition in different excitability states.

The paired-pulse transcranial magnetic stimulation (TMS) paradigm is increasingly employed to examine intracortical inhibitory processes in different motor tasks. Short-interval intracortical inhibition (SICI) has been shown to vary with the size of the MEP elicited by the test TMS pulse. This suggests that factors that alter MEP size, such as changes in cortical excitability, may confound the interpretation of SICI. However, the effect of excitability on SICI has not been systematically investigated. The present study examined SICI in 11 volunteers. The effect of test TMS intensities ranging from 90 to 150% resting motor threshold (RMT) on SICI was examined in three excitability states in the right first dorsal interosseous muscle: rest, isometric abduction of the left index finger (Contra) and isometric abduction of the right index finger (Active). For all excitability states SICI was not observed when test TMS intensity was less than 110% resting motor threshold. This was true even for the Active condition in which 90 and 100% test TMS intensities elicited large and consistent MEPs. For all conditions moderately suprathreshold test TMS intensities (110–120% RMT) yielded the greatest measure of SICI; increasing test TMS intensities resulted in a progressive reduction in the estimate of SICI. These results suggest that estimates of SICI are systematically affected by the intensity of the test TMS pulse, regardless of excitability state. The results suggest that SICI should be examined using a constant test TMS intensity regardless of changes in cortical excitability and test MEP size.

Traumatic brain injury, major depression, and diffusion tensor imaging: Making connections ☆

UNLABELLED It is common for depression to develop after traumatic brain injury (TBI), yet despite poorer recovery, there is a lack in our understanding of whether post-TBI brain changes involved in depression are akin to those in people with depression without TBI. Modern neuroimaging has helped recognize degrees of diffuse axonal injury (DAI) as being related to extent of TBI, but its ability to predict long-term functioning is limited and has not been considered in the context of post-TBI depression. A more recent brain imaging technique (diffusion tensor imaging; DTI) can measure the integrity of white matter by measuring the directionality or anisotropy of water molecule diffusion along the axons of nerve fibers. AIM To review DTI results in the TBI and depression literatures to determine whether this can elucidate the etiology of the development of depression after TBI. METHOD We reviewed the TBI/DTI (40 articles) and depression/DTI literatures (17 articles). No articles were found that used DTI to investigate depression post-TBI, although there were some common brain regions identified between the TBI/DTI and depression/DTI studies, including frontotemporal, corpus callosum, and structures contained within the basal ganglia. Specifically, the internal capsule was commonly reported to have significantly reduced fractional anisotropy, which agrees with deep brain stimulation studies. CONCLUSION It is suggested that measuring the degree of DAI by utilizing DTI in those with or without depression post-TBI, will greatly enhance prediction of functional outcome.

Exploring the optimal site for the localization of dorsolateral prefrontal cortex in brain stimulation experiments

BACKGROUND Dorsolateral prefrontal cortex (DLPFC) is a common target for repetitive transcranial magnetic stimulation (rTMS) experiments and therapeutic protocols. OBJECTIVE The aim of this study was to investigate the optimal method for the localization of DLPFC for use in these studies. METHODS Twelve healthy subjects underwent a structural magnetic resonance imaging (MRI) scan, a TMS procedure to establish the location of the motor cortex and a neuronavigational procedure to assess the relative position of the DLPFC. Several electroencephalographic (EEG) points and a position 5 cm anterior to motor cortex were established. RESULTS The DLPFC site used was identified as being approximately halfway between the EEG points F3 and AF3. This point is considerably more anterior than the point identified by measuring 5 cm anterior to motor cortex. CONCLUSIONS EEG points provide a useful way to optimally identify DLPFC.

Removing artefacts from TMS-EEG recordings using independent component analysis: Importance for assessing prefrontal and motor cortex network properties

INTRODUCTION The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is emerging as a powerful tool for causally investigating cortical mechanisms and networks. However, various artefacts contaminate TMS-EEG recordings, particularly over regions such as the dorsolateral prefrontal cortex (DLPFC). The aim of this study was to substantiate removal of artefacts from TMS-EEG recordings following stimulation of the DLPFC and motor cortex using independent component analysis (ICA). METHODS 36 healthy volunteers (30.8 ± 9 years, 9 female) received 75 single TMS pulses to the left DLPFC or left motor cortex while EEG was recorded from 57 electrodes. A subset of 9 volunteers also received 50 sham pulses. The large TMS artefact and early muscle activity (-2 to ~15 ms) were removed using interpolation and the remaining EEG signal was processed in two separate ICA runs using the FastICA algorithm. Five sub-types of TMS-related artefacts were manually identified: remaining muscle artefacts, decay artefacts, blink artefacts, auditory-evoked potentials and other noise-related artefacts. The cause of proposed blink and auditory-evoked potentials was assessed by concatenating known artefacts (i.e. voluntary blinks or auditory-evoked potentials resulting from sham TMS) to the TMS trials before ICA and evaluating grouping of resultant independent components (ICs). Finally, we assessed the effect of removing specific artefact types on TMS-evoked potentials (TEPs) and TMS-evoked oscillations. RESULTS Over DLPFC, ICs from proposed muscle and decay artefacts correlated with TMS-evoked muscle activity size, whereas proposed TMS-evoked blink ICs combined with voluntary blinks and auditory ICs with auditory-evoked potentials from sham TMS. Individual artefact sub-types characteristically distorted each measure of DLPFC function across the scalp. When free of artefact, TEPs and TMS-evoked oscillations could be measured following DLPFC stimulation. Importantly, characteristic TEPs following motor cortex stimulation (N15, P30, N45, P60, N100) could be recovered from artefactual data, corroborating the reliability of ICA-based artefact correction. CONCLUSIONS Various different artefacts contaminate TMS-EEG recordings over the DLPFC and motor cortex. However, these artefacts can be removed with apparent minimal impact on neural activity using ICA, allowing the study of TMS-evoked cortical network properties.

Hippocampal volumetrics in treatment-resistant depression and schizophrenia: The devil's in De-Tail†

Studies of patients with major depressive disorder (MDD) and schizophrenia (SCH) have revealed reduced hippocampal volumes, but findings have been inconsistent due to sample and measurement differences. The current study sought to measure this structure in a large sample of MDD, SCH, and healthy subjects, using a strict measurement protocol, to elucidate morphological‐specific volumetric differences. Patients with treatment‐resistant MDD (N = 182) and treatment‐resistant SCH with auditory‐verbal hallucinations (N = 52), and healthy controls (N = 76) underwent psychiatric assessments and brain MRI. The findings indicate that (1) MDD and SCH patients have reduced total hippocampal volume which was marked in the tails (more so in patients with MDD), (2) region of interest estimation protocols and sample characteristics may help explain volumetric differences between previous SCH studies.

Individualized Alpha Activity and Frontal Asymmetry in Major Depression

Lateralized differences in frontal alpha power in individuals with major depressive disorder (MDD) are thought to reflect an aberrant affective processing style. However research into anterior alpha asymmetry and MDD has often produced conflicting results. The current study aimed to investigate whether individualized alpha bandwidths provide a more sensitive measure of anterior alpha asymmetry in MDD than the traditional fixed 8–13 Hz alpha band. Resting EEG was recorded from 34 right-handed female participants (18 controls, 16 MDD). Each participants Individual Alpha Frequency was used to delineate a broad individualized alpha band and three individualized narrow alpha sub-bands: lower alpha1, lower alpha 2 and upper alpha. Activity within the broad and narrow individualized bandwidths and within the traditional fixed alpha band were used to compare a) controls and acutely depressed individuals and b) medicated and unmedicated MDD participants. Individualizing and subdividing the alpha bandwidth did not add appreciably to the sensitivity of anterior alpha asymmetry in MDD as no significant differences in lateralized alpha power between controls and MDD participants were observed in any alpha bandwidth. This finding was consistent under two reference schemes and across multiple scalp locations. Within the MDD group, antidepressant use was associated with significantly greater right than left hemispheric power in the lower alpha 1 band. The relevance of this finding is discussed in relation to the electrophysiological correlates of antidepressant medication use, lateralized differences in affective processing and treatment resistant MDD.

Volumetric, cortical thickness and white matter integrity alterations in bipolar disorder type I and II.

BACKGROUND Bipolar disorder (BD) is a debilitating psychiatric disorder affecting millions of people worldwide with mean time to diagnosis estimated to be at least 10 years. Whilst many brain imaging studies have compared those with BD to controls, few have attempted to investigate differences between BD Type I and II and matched controls. METHODS Thirty-one patients with BD (16 Type I and 15 Type II) and 31 matched healthy controls were MRI brain scanned with conventional T1-weighted and diffusion tensor imaging methods. RESULTS There was significantly reduced regional brain volume and thickness among the BD subjects, but also between BD Type I when compared to Type II. White matter integrity also differed between the groups and BD severity correlated significantly with regional brain volume and thickness. LIMITATIONS Future investigations will consider length of time each BD patient had been diagnosed with BD, as well as assessing controls for family history of psychiatric illness, specifically BD. Similarly, genetic assessment will be conducted as well. CONCLUSIONS These findings suggest that there are not only regional brain volumetric, thickness and white matter integrity differences between BD and matched controls, but also between those with BD Type I and Type II, such that reduced regional brain volume may underlie BD Type I whereas white matter integrity is more altered in BD Type II.

Attentional influences on short-interval intracortical inhibition.

OBJECTIVE The allocation of attention to sensory stimulation and movement might influence cortical activity. Two experiments were conducted to investigate the effect of variation of intensity of attention (Experiment 1) and direction of attention (Experiment 2) on cortical excitability and short-interval intracortical inhibition (SICI) during performance of a simple index finger abduction task. METHODS Subjects responded to subtle cutaneous electrical stimulation delivered to the index finger while single and paired TMS pulses were delivered during muscle relaxation between successive responses. In Experiment 1, attentional resources allocated to the task were manipulated using a dual task paradigm involving a backward-counting task. In Experiment 2, spatial attention was varied by delivering cutaneous stimuli to the responding or the non-responding index finger. RESULTS In Experiment 1, SICI was reduced during performance, but was unaffected by variation in the intensity of attention. The results of Experiment 2, however, showed that SICI was significantly lower when attention was directed to the responding hand compared with when it was directed to the non-responding hand. CONCLUSIONS While SICI was not affected by variation of attentional resources, it was influenced by spatial attention. SIGNIFICANCE These findings may be relevant in future investigations of the underlying neurophysiology of plasticity.

Analysing concurrent transcranial magnetic stimulation and electroencephalographic data: A review and introduction to the open-source TESA software

ABSTRACT The concurrent use of transcranial magnetic stimulation with electroencephalography (TMS–EEG) is growing in popularity as a method for assessing various cortical properties such as excitability, oscillations and connectivity. However, this combination of methods is technically challenging, resulting in artifacts both during recording and following typical EEG analysis methods, which can distort the underlying neural signal. In this article, we review the causes of artifacts in EEG recordings resulting from TMS, as well as artifacts introduced during analysis (e.g. as the result of filtering over high‐frequency, large amplitude artifacts). We then discuss methods for removing artifacts, and ways of designing pipelines to minimise analysis‐related artifacts. Finally, we introduce the TMS–EEG signal analyser (TESA), an open‐source extension for EEGLAB, which includes functions that are specific for TMS–EEG analysis, such as removing and interpolating the TMS pulse artifact, removing and minimising TMS‐evoked muscle activity, and analysing TMS‐evoked potentials. The aims of TESA are to provide users with easy access to current TMS–EEG analysis methods and to encourage direct comparisons of these methods and pipelines. It is hoped that providing open‐source functions will aid in both improving and standardising analysis across the field of TMS–EEG research. HIGHLIGHTSTMS pulses result in numerous artifacts in concurrent EEG recordings.We review the origins of these artifacts and methods for removing them.We also introduce TESA, an open‐source EEGLAB extension for TMS‐EEG analysis.

The (Eigen)Value of Diffusion Tensor Imaging to Investigate Depression After Traumatic Brain Injury

Background: Many people with a traumatic brain injury (TBI), even mild to moderate, will develop major depression (MD). Recent studies of patients with MD suggest reduced fractional anisotropy (FA) in dorsolateral prefrontal cortex (DLPFC), temporal lobe tracts, midline, and capsule regions. Some of these pathways have also been found to have reduced FA in patients with TBI. It is unknown whether the pathways implicated in MD after TBI are similar to those with MD without TBI. This study sought to investigate whether there were specific pathways unique to TBI patients who develop MD. Methods: A sample of TBI‐MD subjects (N = 14), TBI‐no‐MD subjects (N = 12), MD‐no‐TBI (N = 26), and control subjects (no TBI or MD, N = 23), using a strict measurement protocol underwent psychiatric assessments and diffusion tensor brain Magnetic Resonance Imaging (MRI). Results: The findings of this study indicate that (1) TBI patients who develop MD have reduced axial diffusivity in DLPFC, corpus callosum (CC), and nucleus accumbens white matter tracts compared to TBI patients who do not develop MD and (2) MD patients without a history of TBI have reduced FA along the CC. We also found that more severe MD relates to altered radial diffusivity. Conclusions: These findings suggest that compromise to specific white matter pathways, including both axonal and myelination aspects, after a mild TBI underlie the susceptibility of these patients developing MD. Hum Brain Mapp 35:227–237, 2014.