Factors to consider when applying transcranial magnetic stimulation of dorsolateral prefrontal cortex when resting motor threshold is asymmetric: A case study.

Transcranial magnetic stimulation (TMS) is an increasingly popular tool in treating psychiatric conditions. The dorsal lateral prefrontal cortex (DLPFC) is typically targeted for stimulation, with magnetic field intensity being calibrated by establishing resting motor threshold (RMT) at hand region of primary motor cortex (M1 hand). This presumes that scalp-to-cortex distance (SCD) and cortical thickness is similar at both sites. We present data from a patient who had very asymmetrical RMTs (47 and 78). We investigated SCDs in this patient at the M1 hand and DLPFC, and the M1 hand cortical thickness. We also investigated TMS electric field distribution. The M1 hand SCD and cortical thickness of the M1 hand was larger on the side with higher RMT. Electric field finite element modelling demonstrated the focal point did not effectively reach the M1 hand with higher RMT as the postcentral gyrus was shunting it. Hence, successful DLPFC treatment was based upon the side with lower RMT. This study highlights the importance of tailoring DLPFC treatment intensity not only based on RMT at the M1 hand, and upon the degree to which SCD distance differs between sites, but also based upon size, shape, and density of M1 hand, as well as electric field distribution.

Occipital bending in depression.

There are reports of differences in occipital lobe asymmetry within psychiatric populations when compared with healthy control subjects. Anecdotal evidence and enlarged lateral ventricles suggests that there may also be a different pattern of curvature whereby one occipital lobe wraps around the other, termed 'occipital bending'. We investigated the prevalence of occipital bending in 51 patients with major depressive disorder (males mean age = 41.96 ± 14.00 years, females mean age = 40.71 ± 12.41 years) and 48 age- and sex-matched healthy control subjects (males mean age = 40.29 ± 10.23 years, females mean age = 42.47 ± 14.25 years) and found the prevalence to be three times higher among patients with major depressive disorder (18/51, 35.3%) when compared with control subjects (6/48, 12.5%). The results suggest that occipital bending is more common among patients with major depressive disorder than healthy subjects, and that occipital asymmetry and occipital bending are separate phenomena. Incomplete neural pruning may lead to the cranial space available for brain growth being restricted, or ventricular enlargement may exacerbate the natural occipital curvature patterns, subsequently causing the brain to become squashed and forced to 'wrap' around the other occipital lobe. Although the clinical implications of these results are unclear, they provide an impetus for further research into the relevance of occipital bending in major depression disorder.

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.

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.

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.

Does Exposure to Diagnostic Ultrasound Modulate Human Nerve Responses to Magnetic Stimulation?

Ultrasound (US) at diagnostic frequency and power is known to alter nerve potentials; however, the precise mechanism of action is unknown. We investigated whether US alters resting nerve potential to lower the threshold for magnetic nerve stimulation. Seventeen healthy subjects were recruited. For each subject, a 1.5 MHz US imaging probe was placed onto the elbow with the beam directed at the ulnar nerve. The probe was coupled to the skin using standard acoustic coupling gel as would be done for a routine clinical US scan. Ulnar nerve stimulation was performed simultaneously with magnetic stimulation (MS). Successful magnetic stimulation of the ulnar nerve was confirmed with nerve potentials measured by electromyography. There was no significant change in electromyography signal when MS was performed during US exposure. US at the diagnostic frequency and power tested does not alter nerve thresholds with MS. Testing at other frequencies is required, however, before US is negated as a technique to modify MS thresholds.

Volumetrics relate to the development of depression after traumatic brain injury.

Previous research suggests that many people who sustain a traumatic brain injury (TBI), even of the mild form, will develop major depression (MD). We previously reported white matter integrity differences between those who did and did not develop MD after mild TBI. In this current paper, we aimed to investigate whether there were also volumetric differences between these groups, as suggested by previous volumetric studies in mild TBI populations. A sample of TBI-with-MD subjects (N=14), TBI-without-MD subjects (N=12), MD-without-TBI (N=26) and control subjects (no TBI or MD, N=23), received structural MRI brain scans. T1-weighted data were analysed using the Freesurfer software package which produces automated volumetric results. The findings of this study indicate that (1) TBI patients who develop MD have reduced volume in temporal, parietal and lingual regions compared to TBI patients who do not develop MD, and (2) MD patients with a history of TBI have decreased volume in the temporal region compared to those who had MD but without a history of TBI. We also found that more severe MD in those with TBI-with-MD significantly correlated with reduced volume in anterior cingulate, temporal lobe and insula. These findings suggest that volumetric reduction to specific regions, including parietal, temporal and occipital lobes, after a mild TBI may underlie the susceptibility of these patients developing major depression, in addition to altered white matter integrity.

Hippocampal sulcal cavities in depression and healthy individuals.

BACKGROUND: A literature review suggested age and cognitive problems to be related to an increased prevalence of small areas of signal variation within the hippocampus observed on MRI, described as hippocampal sulcal cavities (HSCs; (Maller et al., 2011)). The current study aimed to describe the prevalence of HSCs in patients with treatment-resistant depression (TRD) and healthy controls over a large age-range. METHODS: 115 TRD patients and 86 controls underwent MRI brain scanning. Right and left HSCs were rated separately for prevalence and length. RESULTS: HSCs were observed in 73.04% of those with TRD, statistically more prevalent (p=0.001) than amongst controls (51.16%). These findings are consistent with our review (66% prevalence in memory disorders and 47% in healthy controls). Furthermore, HSC presence and length was associated with aging. LIMITATIONS: The study was cross-sectional so its implications for aging are tentative. A larger sample scanned longitudinally will allow for more sophisticated statistical methods by which to investigate the relationship between HSCs, aging, and TRD. CONCLUSIONS: Although their clinical significance remains uncertain, the results of the current study suggest that HSCs are related with age and those with TRD have more aged brains than their peers.

Hippocampal sulcal cavities: prevalence, risk factors and relationship to memory impairment.

While hippocampal volumes have been extensively examined in neuropsychiatric disorders and ageing, small areas of signal variation within the hippocampus commonly observed on MRI, described as hippocampal sulcal cavities (HSCs), have received less attention. We review the published literature on HSCs to examine their prevalence, putative aetiological factors such as hypertension, and possible cognitive correlates. HSCs were reported in 77% (66% weighted mean) of patients with memory disorders and 48% (47% weighted mean) of controls, and the prevalence increased with age in healthy subjects (r=0.64, p=0.047). A number of studies reported hypertension as a risk factor, and related their presence to poorer memory function. Further work is needed to fully understand the clinical significance of these lesions.

Speech versus non-speech as irrelevant sound: controlling acoustic variation.

Functional differences between speech and non-speech within the irrelevant sound effect were investigated using repeated and changing formats of irrelevant sounds in the form of intelligible words and unintelligible signal correlated noise (SCN) versions of the words. Event-related potentials were recorded from 25 females aged between 18 and 25 while they completed a serial order recall task in the presence of irrelevant sound or silence. As expected and in line with the changing-state hypothesis both words and SCN produced robust changing-state effects. However, words produced a greater changing-state effect than SCN indicating that the spectral detail inherent within speech accounts for the greater irrelevant sound effect and changing-state effect typically observed with speech. ERP data in the form of N1 amplitude was modulated within some irrelevant sound conditions suggesting that attentional aspects are involved in the elicitation of the irrelevant sound effect.

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.