The Effect of Stimulus Parameters on TMS–EEG Muscle Artifacts

BackgroundWhen transcranial magnetic stimulation (TMS) is delivered close to the lateral aspects of the head, large-amplitude (～10–1000 μV) biphasic electroencephalographic (EEG) deflections, peaking at around 4–10 and 8–20 ms, appear.ObjectiveTo characterize the spatiotemporal features of these artifacts, to quantify the effect of stimulus parameters on them, and thus, to study the feasibility of different measurement procedures to decrease the artifacts online. Furthermore, to show that these deflections, when measured with a sample-and-hold system, mainly result from excitation of cranial muscles.MethodsThree subjects received TMS to 16 sites over the left hemisphere. TMS-compatible EEG was recorded simultaneously. Four other subjects received TMS to M1 with different coil rotation and tilt angles and stimulation intensities. We also stimulated a conductive phantom and recorded simultaneous EEG to exclude the possibility of residual electromagnetic artifacts.ResultsThe artifacts were largest when the stimulator was placed above cranial muscles, whereas stimulation of relatively central sites far from the muscles produced muscle artifact-free data. The laterally situated EEG channels were most severely contaminated. The artifacts were significantly reduced when reducing the intensity or when tilting or rotating the coil so that coil wings moved further away from the temporal muscle, while brain responses remained visible. Stimulation of the phantom did not produce such large-amplitude biphasic artifacts.ConclusionAltering the stimulation parameters can reduce the described artifact, while brain responses can still be recorded. The early, laterally appearing, large biphasic TMS-evoked EEG deflections recorded with a sample-and-hold system are caused by cranial muscle activation.     

Clinical utility and prospective of TMS–EEG

Concurrent transcranial magnetic stimulation and electroencephalography (TMS–EEG) has emerged as a powerful tool to non-invasively probe brain circuits in humans, allowing for the assessment of several cortical properties such as excitability and connectivity. Over the past decade, this technique has been applied to various clinical populations, enabling the characterization and development of potential TMS–EEG predictors and markers of treatments and of the pathophysiology of brain disorders. The objective of this article is to present a comprehensive review of studies that have used TMS–EEG in clinical populations and to discuss potential clinical applications. To provide a technical and theoretical framework, we first give an overview of TMS–EEG methodology and discuss the current state of knowledge regarding the use of TMS–EEG to assess excitability, inhibition, plasticity and connectivity following neuromodulatory techniques in the healthy brain. We then review the insights afforded by TMS–EEG into the pathophysiology and predictors of treatment response in psychiatric and neurological conditions, before presenting recommendations for how to address some of the salient challenges faced in clinical TMS–EEG research. Finally, we conclude by presenting future directions in line with the tremendous potential of TMS–EEG as a clinical tool.     

Developmental trajectories of cortical–subcortical interactions underlying the evaluation of trust in adolescence

Social decision making is guided by the ability to intuitively judge personal attributes, including analysis of facial features to infer the trustworthiness of others. Although the neural basis for trustworthiness evaluation is well characterized in adults, less is known about its development during adolescence. We used event-related functional magnetic resonance imaging to examine age-related changes in neural activation and functional connectivity during the evaluation of trust in faces in a sample of adolescent females. During scanning, participants viewed masked presentations of faces and rated their trustworthiness. Parametric modeling of trust ratings revealed enhanced activation in amygdala and insula to untrustworthy faces, effects which peaked during mid-adolescence. Analysis of amygdala functional connectivity demonstrated enhanced amygdala–insula coupling during the evaluation of untrustworthy faces. This boost in connectivity was attenuated during mid-adolescence, suggesting a functional transition within face-processing circuits. Together, these findings underscore adolescence as a period of reorganization in neural circuits underlying socioemotional behavior.     

The contribution of charcoal burning to the rise and decline of suicides in Hong Kong from 1997–2007

Background  

There has been scant research exploring the relationship between choice of method (means) of self-inflicted death, and broader social or contextual factors. The recent emergence and growth of suicide using carbon monoxide poisoning resulting from burning charcoal in an enclosed space (hereafter, “charcoal burning”) was related to an increase in the overall suicide rate in Hong Kong. The growth of this method coincided with changing economic conditions. This paper expands upon previous work to explore possible relationships further.     

Short-Latency Artifacts Associated with Concurrent TMS–EEG

BackgroundConcurrent transcranial magnetic stimulation and electroencephalography (TMS–EEG) is an emerging method for studying cortical network properties. However, various artifacts affect measurement of TMS-evoked cortical potentials (TEPs), especially within 30 ms of stimulation.Objective/hypothesisThe aim of this study was to assess the origin and recovery of short-latency TMS–EEG artifacts (<30 ms) using different stimulators and under different experimental conditions.MethodsEEG was recorded during TMS delivered to a phantom head (melon) and 12 healthy volunteers with different TMS machines, at different scalp positions, at different TMS intensities, and following paired-pulse TMS. Recovery from the TMS artifact and other short-latency artifacts were compared between conditions.ResultsFollowing phantom stimulation, the artifact resulting from different TMS machines (Magstim 200, Magventure MagPro R30 and X100) and pulse shapes (monophasic and biphasic) resulted in different artifact profiles. After accounting for differences between machines, TMS artifacts recovered within ～12 ms. This was replicated in human participants, however a large secondary artifact (peaks at 5 and 10 ms) became prominent following stimulation over lateral scalp positions, which only recovered after ～25–40 ms. Increasing TMS intensity increased secondary artifact amplitude over both motor and prefrontal cortex. There was no consistent modulation of the secondary artifact following inhibitory paired-pulse TMS (interstimulus interval = 100 ms) over motor cortex.ConclusionsThe secondary artifact observed in humans is consistent with activation of scalp muscles following TMS. TEPs can be recorded within a short period of time (10–12 ms) following TMS, however measures must be taken to avoid muscle stimulation.     

Reduced cortical folding of the anterior cingulate cortex in obsessive–compulsive disorder

Background

Anterior cingulate cortex (ACC) abnormalities have been implicated consistently in the pathophysiology of obsessive–compulsive disorder (OCD), yet it remains unclear whether these abnormalities originated during early neurodevelopment. In this study, we examined the ACC sulcal/gyral patterns to investigate whether neurodevelopmental anomalies of the ACC were present in patients with OCD. We hypothesized that patients with OCD would show reduced cortical folding of the ACC compared with controls.

Methods

We used magnetic resonance imaging (MRI) of 169 healthy volunteers and 110 patients with OCD to examine the paracingulate sulcus and cingulate sulcus. We assessed cortical folding patterns according to established classification criteria and constructed 3 categories of paracingulate sulcus morphology according to its presence and anteroposterior extent: “prominent,” “present” and “absent.” We classified the cingulate sulcus as “interrupted” or “continuous” according to the interruptions in its course. In addition, we evaluated ACC sulcal asymmetry based on interhemispheric comparisons of paracingulate sulcus morphology.

Results

Analyses revealed that patients with OCD were significantly less likely than controls to show a well-developed left paracingulate sulcus: 50.0% of patients and 65.1% of controls showed a “prominent” or “present” paracingulate sulcus in the left hemisphere. However, there were no differences in regard to cingulate sulcus continuity, and patients also showed the same leftward ACC sulcal asymmetry as controls.

Limitations

Our study was limited by the fact that we obtained the MRI scans from 2 different scanners, and we did not calculate cerebral fissurization as our study was restricted to 1 specific brain region. Moreover, patients and controls differed significantly in terms of sex ratio and IQ, although we controlled these variables as covariates.

Conclusion

Our findings imply a subtle deviation in the early neurodevelopment of the ACC in patients with OCD, but the extent to which these anomalies contributed to the pathogenesis of OCD remains unclear. Further studies that link the ACC morphologic anomalies to the pathophysiology of OCD are recommended.     

The “business” metaphor in the delivery of human services

A critique is presented of the application of business concepts to the delivery of human services. It is first established that such application involves the use of a metaphor. Some notions of how metaphors function are then presented and used to describe how the business metaphor may operate in its application to the delivery of mental health services. Both potential benefits and problems that may result from such an application are discussed. It is concluded that business is not an appropriate metaphor for the delivery of human services.The author wishes to thank Dr. Seymour Friedland for his encouragement and for his helpful criticisms and comments.     

The contribution of sensory–regulatory markers to the accuracy of ASD screening at 12 months

Screening tools for autism spectrum disorders (ASD) focus primarily on identifying early-emerging social–communication markers. This study's objective was to examine the predictive validity of the First Year Inventory (FYI) risk cutoffs, including the sensory–regulatory domain.Parents of 613 12-month infants completed the FYI, an ASD screening questionnaire. Norm-based FYI risk criteria with and without the sensory–regulatory domain were evaluated. Infants at social–communication risk (n = 10), at social–communication and sensory–regulatory risk (n = 19), and a subset of infants at no risk (n = 60) were followed at 13 and 30 months. Children were referred for further evaluation as needed. The FYI identified 60% of those with ASD, and 87.5% of those with other types of developmental problems at 30 months within the followed sample. Applying the FYI dual risk criteria led to higher specificity relative to mean risk and social risk alone. Infants with dual risk had the highest rate of persisting referral for evaluation. Infants with dual risk and those with only social risk had lower developmental scores particularly in the social–communication domain compared to those with no risk. Including sensory–regulatory markers in screening for ASD leads to the identification of children with persisting and pervasive clinical needs and reduces false positive rates.     

Altered 13C glucose metabolism in the cortico–striato–thalamo–cortical loop in the MK-801 rat model of schizophrenia

Using a modified MK-801 (dizocilpine) N-methyl--aspartic acid (NMDA) receptor hypofunction model for schizophrenia, we analyzed glycolysis, as well as glutamatergic, GABAergic, and monoaminergic neurotransmitter synthesis and degradation. Rats received an injection of MK-801 daily for 6 days and on day 6, they also received an injection of [1-¹³C]glucose. Extracts of frontal cortex (FCX), parietal and temporal cortex (PTCX), thalamus, striatum, nucleus accumbens (NAc), and hippocampus were analyzed using ¹³C nuclear magnetic resonance spectroscopy, high-performance liquid chromatography, and gas chromatography–mass spectrometry. A pronounced reduction in glycolysis was found only in PTCX, in which ¹³C labeling of glucose, lactate, and alanine was decreased. ¹³C enrichment in lactate, however, was reduced in all areas investigated. The largest reductions in glutamate labeling were detected in FCX and PTCX, whereas in hippocampus, striatum, and Nac, ¹³C labeling of glutamate was only slightly but significantly reduced. The thalamus was the only region with unaffected glutamate labeling. γ-Aminobutyric acid (GABA) labeling was reduced in all areas, but most significantly in FCX. Glutamine and aspartate labeling was unchanged. Mitochondrial metabolites were also affected. Fumarate labeling was reduced in FCX and thalamus, whereas malate labeling was reduced in FCX, PTCX, striatum, and NAc. Dopamine turnover was decreased in FCX and thalamus, whereas that of serotonin was unchanged in all regions. In conclusion, neurotransmitter metabolism in the cortico–striato–thalamo–cortical loop is severely impaired in the MK-801 (dizocilpine) NMDA receptor hypofunction animal model for schizophrenia.     

Ibuprofen treatment modifies cortical sources of EEG rhythms in mild Alzheimer’s disease

ObjectiveNon-steroidal anti-inflammatory drugs such as ibuprofen have a protective role on risk of Alzheimer’s disease (AD). Here we evaluated the hypothesis that long-term ibuprofen treatment affects cortical sources of resting electroencephalographic (EEG) rhythms in mild AD patients.MethodsTwenty-three AD patients (13 treated AD IBUPROFEN; 10 untreated AD PLACEBO) were enrolled. Resting EEG data were recorded before and 1 year after the ibuprofen/placebo treatment. EEG rhythms were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). LORETA was used for EEG source analysis.ResultsIn the AD PLACEBO group, amplitude of delta sources was globally greater at follow-up than baseline. Instead, amplitude of delta sources remained stable or decreased in the majority of the AD IBUPROFEN patients. Clinical (CDR) but not global cognitive status (MMSE) reflected EEG results.ConclusionsThese results suggest that in mild AD patients, a long-term ibuprofen treatment slightly slows down the progressive increment of delta rhythms as a sign of contrast against the neurodegenerative processes.SignificanceThey motivate future investigations with larger population and extended neuropsychological testing, to study the relationships among ibuprofen treatment, delta cortical sources, and higher order functions.     

Correlation of risk-taking propensity with cross-frequency phase–amplitude coupling in the resting EEG

Objective

Recent evidence has suggested that the weak inhibitory influence of the prefrontal cortex on the subcortical structures may be responsible for risk-taking behaviour. The aim was to determine the possibility that this weakness in top-down control is reflected in changes in the cross-frequency phase–amplitude coupling (CFPAC) in the electroencephalography (EEG).

Methods

Nineteen-channel EEGs were recorded from 50 healthy volunteers with their eyes closed before risk-taking propensity was assessed by behavioural measures, the domain-specific risk-taking (DOSPERT) scale and the Barrett impulsiveness scale (BIS). Correlation analyses between the CFPACs and the behavioural measures were performed.

Results

The CFPACs were negatively correlated with the risk-taking DOSPERT and BIS scores in frontal (Fp2) and centro–parietal (C3, C4 and P4) regions. By contrast, the CFPACs were positively correlated with the risk-taking DOSPERT and BIS scores in the right hemisphere (T8 and P8).

Conclusions

We suggest that frequent risk-taking behaviour is closely associated with the reduced interference of the cortical control network on the reward-oriented system. The CFPAC, which reflects the degree of interactions among functional systems, provides information about an individual’s risk-taking propensity.

Significance

The CFPAC may be a useful neurophysiological indicator of an individual’s tendency towards risk-taking behaviours, which thus potentially contributes to evaluating the severity of the psychiatric diseases exhibiting abnormal risk-taking behaviours.     

Electrophysiological properties of hippocampal–cortical neural networks,role in the processes of learning and memory in rats

The recording of hippocampal and cortical long-term potentiation (LTP) in rats in vivo is an appropriate and commonly used method to describe changes in cellular mechanisms underlying synaptic plasticity. Recently, we introduced a method for the simultaneous recording of LTP in bilateral CA1 regions and parietal association cortex (PtA), and observed differences between the Schaffer collateral–CA1 pathway (SC), Schaffer collateral/associational commissural pathway (SAC) and Schaffer collateral/associational commissural–cortex pathway (SACC). In this study, we found that (1) synaptic transmission of the SAC and SACC pathways depended on hippocampal commissural fibers [dorsal and ventral hippocampal commissural fibers, the medial septum (MS) and hippocampal CA3 commissural fibers], (2) nerve conduction velocity of the SACC pathway might be higher than that of the SAC pathway, (3) the input/output (I/O) curve of the SC pathway was shifted to the left side, compared to that of the SAC and SACC pathways, (4) all three pathways could induce stable LTP; however, LTP of the SAC and SACC pathways was much stronger than that of the SC pathway, (5) the degree of paired-pulse facilitation (PPF) was weaker in the SC pathway than that in the SAC and SACC pathways, (6) after cutting off the corpus callosum and commissural fibers, spatial learning and memory were impaired, and the ability to explore the novel environment and spontaneous locomotor activity were weakened. Taken together, our results suggested that hippocampal commissural fibers were very important for exchanging information between hemispheres, and basic differences in electrophysiological properties of hippocampal–cortical neural networks play a vital role in the processes of learning and memory.     

Visual and semiautomated evaluation of epileptogenicity in focal cortical dysplasias — An intracranial EEG study

IntroductionThe aim of the study was the evaluation of the added value of depth to subdural electrodes in delineating epileptogenicity of focal cortical dysplasias (FCDs) and to test the Epileptogenicity Index (EI) in this setting.Material and methodsFifteen patients with FCD underwent iEEG with subdural and depth electrodes. Visual/EI analysis was performed in up to three habitual seizures per patient.ResultsVisual analysis: Grid onset seizures (n = 10) started in electrodes overlying the lesion in 7 and remote from it in 3 cases. Depth onset seizures (n = 7) affected only intralesional contacts in 4, intra- and extralesional in 2, and exclusively extralesional in 1 patient. Seizures started in depth and grid contacts simultaneously in 2 cases.EI analysis: The EI completely confirmed visual localization of seizure onset in 8 cases and depicted ictal onset-time accurately in 13. Beta/gamma ictal patterns were most reliably captured.Impact on surgical decision: Resection outline differed from MRI lesion in 7 patients based on grid and in three based on depth electrode information.DiscussionIn FCD, seizures can be generated within gyral/deep tissue appearing normal on imaging.ConclusionInvestigating FCD with subdural and depth electrodes is efficient to outline the seizure onset zone. The EI is a helpful additional tool to quantify epileptogenicity. Specific ictal patterns are prerequisite for reliable results.     

Chimera RNA interference knockdown of γ-synuclein in human cortical astrocytes results in mitotic catastrophe

Elevated levels of γ-synuclein(γ-syn)expression have been noted in the progression of glioblastomas,and also in the cerebrospinal fluid of patients diagnosed with neurodegenerative diseases.γ-Syn can be either internalized from the extracellular milieu or expressed endogenously by human cortical astrocytes.Internalizedγ-syn results in increased cellular proliferation,brain derived neurotrophic factor release and astroprotection.However,the function of endogenousγ-syn in primary astrocytes,and the relationship to these two opposing disease states are unknown.γ-Syn is expressed by astrocytes in the human cortex,and to gain a better understanding of the role of endogenous γ-syn,primary human cortical astrocytes were treated with chimera RNA interference(RNAi)targeting γ-syn after release from cell synchronization.Quantitative polymerase chain reaction analysis demonstrated an increase in endogenousγ-syn expression 48 hours after release from cell synchronization,while RNAi reduced γ-syn expression to control levels.Immunocytochemistry of Ki67 and 5-bromodeoxyuridine showed chimera RNAi γ-syn knockdown reduced cellular proliferation at 24 and 48 hours after release from cell synchronization.To further investigate the consequence of γ-syn knockdown on the astrocytic cell cycle,phosphorylated histone H3 pSer10(pHH3)and phosphorylated cyclin dependent kinase-2 pTyr15(pCDK2)levels were observed via western blot analysis.The results revealed an elevated expression of pHH3,but not pCDK2,indicating γ-syn knockdown leads to disruption of the cell cycle and chromosomal compaction after 48 hours.Subsequently,flow cytometry with propidium iodide determined that increases in apoptosis coincided with γ-syn knockdown.Therefore,γ-syn exerts its effect to allow normal astrocytic progression through the cell cycle,as evidenced by decreased proliferation marker expression,increased pHH3,and mitotic catastrophe after knockdown.In this study,we demonstrated that the knockdown of γ-syn within primary human cortical astrocytes using chimera RNAi leads to cell cycle disruption and apoptosis,indicating an essential role for γ-syn in regulating normal cell division in astrocytes.Therefore,disruption to γ-syn function would influence astrocytic proliferation,and could be an important contributor to neurological diseases.     

Critical implication of the (70–96) domain of human immunodeficiency virus type 1 Vpr protein in apoptosis of primary rat cortical and striatal neurons

The human immunodeficiency virus (HIV)-1 regulatory protein Vpr has been detected in the serum of HIV-seropositive individuals and in the cerebrospinal fluid of acquired immunodeficiency syndrome (AIDS) patients suffering from neurological disorders. Therefore, Vpr could play a critical role in the neuronal apoptosis observed postmortem in the brain of patients, often connected to a severe AIDS-related disease termed HIV-associated dementia (HAD). This suggests that the Vpr neurotoxicity already observed in vitro on hippocampal neurons could also occur in other brain structures. In this study the authors have investigated the ability of synthetic Vpr to induce apoptosis in primary cultures of rat cortical and striatal neurons. Moreover, the authors have explored the Vpr minimal proapoptotic region using synthetic Vpr fragments and mutants of the protein. Treatments of both neuronal types with Vpr, its C-terminal domain, Vpr(52-96), or a shorter fragment, Vpr(70-96), led to dose- and time-dependent cell death as determined by flow cytometry after propidium iodide labeling, phase-contrast microscopy, and TUNEL labeling. Taken together, these results support an apoptosis-induced death of these neurons. The (71-82) Vpr peptide, previously shown toxic to isolated mitochondria, was inactive on neurons. Vpr-induced neuronal apoptosis was associated with activation of caspase-3 beginning 3 h after Vpr extracellular addition and peaking 3 h later. Moreover, an hyperproduction of reactive oxygen species was observed. In addition to hippocampal neurons, the extension of the apoptotic property of Vpr to cortical and striatal neurons could account for several signs observed in HAD and is thus consistent with a possible involvement of Vpr in this syndrome.     

An exploration of the relevance of the concept of “flow” in art therapy

Abstract

Mihaly Csikszentmihalyi, a psychologist, conducted research into the psychological state of happiness. A result of this work is the concept of “flow” (Csikszentmihalyi, 1992 Czikszentmihalyi, M. 1992. “Flow”: The psychology of happiness, USA: Harper & Row.  [Google Scholar]). Csikszentmihalyi's work has to date not been reviewed in art therapy literature for its relevance to our clinical practice or theoretical conceptualisation. Both art therapy and the concept of “flow” are concerned with the well-being of the individual. In this paper I will explore possible intersections between them. I present a summary of the salient features of Csikszentmihalyi's findings in regard to flow and explore how I have found that an understanding of this psychological state can be relevant in my art therapy practice. A consideration of the phenomenon of “flow” may be a way of re-addressing a balance between understanding an art therapy client's areas of “wellness” and “strength” as well as possible areas of “ illness” or “difficulty”.