Emily S. Kappenman

A technical guide to tDCS, and related non-invasive brain stimulation tools.

Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain.

Committee report: Publication guidelines and recommendations for studies using electroencephalography and magnetoencephalography

Electromagnetic data collected using electroencephalography (EEG) and magnetoencephalography (MEG) are of central importance for psychophysiological research. The scope of concepts, methods, and instruments used by EEG/MEG researchers has dramatically increased and is expected to further increase in the future. Building on existing guideline publications, the goal of the present paper is to contribute to the effective documentation and communication of such advances by providing updated guidelines for conducting and reporting EEG/MEG studies. The guidelines also include a checklist of key information recommended for inclusion in research reports on EEG/MEG measures.

The effects of electrode impedance on data quality and statistical significance in ERP recordings

To determine whether data quality is meaningfully reduced by high electrode impedance, EEG was recorded simultaneously from low- and high-impedance electrode sites during an oddball task. Low-frequency noise was found to be increased at high-impedance sites relative to low-impedance sites, especially when the recording environment was warm and humid. The increased noise at the high-impedance sites caused an increase in the number of trials needed to obtain statistical significance in analyses of P3 amplitude, but this could be partially mitigated by high-pass filtering and artifact rejection. High electrode impedance did not reduce statistical power for the N1 wave unless the recording environment was warm and humid. Thus, high electrode impedance may increase noise and decrease statistical power under some conditions, but these effects can be reduced by using a cool and dry recording environment and appropriate signal processing methods.

Reduced capacity but spared precision and maintenance of working memory representations in schizophrenia

CONTEXT Working memory deficits are considered a core feature of schizophrenia. Several recent integrative articles have offered mechanistic computational and neurobiological models of the origins of this cognitive deficit. OBJECTIVE To test predictions of these models using a new experimental paradigm from the basic science literature that makes it possible to determine whether patients with schizophrenia show (1) deficits in working memory storage capacity, (2) deficits in the precision of working memory representations, and (3) an amplification of these deficits as the retention interval increases. DESIGN Case-control design. All subjects performed a color working memory test in which they were asked to recall 3 or 4 items after a 1- or 4-second delay. All subjects also received a standard measure of intelligence and the Matrics Consensus Cognitive Battery. SETTING A tertiary care research outpatient clinic. Patients A total of 31 clinically stable patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder and 26 healthy volunteers participated. The 2 groups were similar in age, sex, and ethnicity distribution. MAIN OUTCOME MEASURES (1) The number of items stored in working memory and (2) the precision of the working memory representations. RESULTS Patients showed a clear reduction in the number of items stored in working memory. Patients did not differ from controls in the precision of their working memory representations. There was no evidence of delay-related amplification of impairment in either capacity or precision. CONCLUSIONS Patients do not show the type of imprecision or delay-dependent amplification of impairment that is predicted on the basis of current models of the neurobiology of schizophrenia. The models need to be revised to account for a pure reduction in the number of items that patients are able to store in working memory.

Behavioral and ERP measures of attentional bias to threat in the dot-probe task: poor reliability and lack of correlation with anxiety

The dot-probe task is often considered a gold standard in the field for investigating attentional bias to threat. However, serious issues with the task have been raised. Specifically, a number of studies have demonstrated that the traditional reaction time (RT) measure of attentional bias to threat in the dot-probe task has poor internal reliability and poor test-retest reliability. In addition, although threatening stimuli capture attention in other paradigms, attentional bias to threat has not usually been found in typical research participants in the dot-probe task. However, when attention is measured in the dot-probe task with the N2pc component of the event-related potential waveform, substantial attentional orienting to threat is observed, and the internal reliability is moderate. To provide a rigorous comparison of the reliability of this N2pc measure and the conventional behavioral measure, as well as to examine the relationship of these measures to anxiety, the present study examined the N2pc in conjunction with RT in the dot-probe task in a large sample of participants (N = 96). As in previous studies, RT showed no bias to threatening images across the sample and exhibited poor internal reliability. Moreover, this measure did not relate to trait anxiety. By contrast, the N2pc revealed a significant initial shift of attention to threat, and this measure was internally reliable. However, the N2pc was not correlated with trait anxiety, indicating that it does not provide a meaningful index of individual differences in anxiety in the dot-probe task. Together, these results indicate a serious need to develop new tasks and methods to more reliably investigate attentional bias to threat and its relationship to anxiety in both clinical and non-clinical populations.

Emotion Regulation Abnormalities in Schizophrenia: Cognitive Change Strategies Fail to Decrease the Neural Response to Unpleasant Stimuli

Contrary to early conceptualizations of emotional experience in schizophrenia (SZ), recent research indicates that patients do not self-report less in-the-moment pleasure than controls (CN). Rather, patients report experiencing elevated levels of negative emotionality in response to a range of evocative stimuli. In this study, we examined the possibility that elevations in negative emotionality in SZ may reflect an underlying emotion regulation abnormality. Event-related potentials (ERPs) were recorded from outpatients with SZ (n = 25) and demographically matched healthy controls (n = 21) during passive viewing of unpleasant and neutral photographs. Unpleasant images were preceded by an audio description that described the image as being either negative or neutral. Neutral images were preceded by neutral audio descriptions. The late positive potential (LPP), an ERP component sensitive to cognitive change strategies, was examined as an index of emotion regulation. Both CN and SZ showed an increased LPP to negatively described unpleasant images compared with neutral images. In addition, CN showed evidence of emotion regulation, as reflected by a smaller LPP for unpleasant images preceded by a neutral descriptor, relative to a negative descriptor. In contrast, SZ patients showed an inability to downregulate emotional response, as evidenced by no difference in the amplitude of the LPP for unpleasant images preceded by negative or neutral descriptors. Findings provide neurophysiological evidence for an emotion regulation abnormality in SZ and suggest that failures in cognitive change may underlie increased negative emotionality in SZ.

Failure of schizophrenia patients to overcome salient distractors during working memory encoding.

BACKGROUND Prior demonstrations of impaired attentional control in schizophrenia focused on conditions in which top-down control is needed to overcome prepotent response tendencies. Attentional control over stimulus processing has received little investigation. Here, we test whether attentional control is impaired during working memory encoding when salient distractors compete with less salient task-relevant stimuli. METHODS Patients with schizophrenia (n = 28) and healthy control subjects (n = 25) performed a visuospatial working memory paradigm in which half of the to-be-encoded stimuli flickered to increase their salience. After a 2-second delay, stimuli reappeared and participants had to decide whether or not a probed item had shifted location. RESULTS In the unbiased condition where flickering and nonflickering stimuli were equally likely to be probed, both groups displayed a trend toward better memory for the flickering items. In the flicker-bias condition in which the flickering stimuli were likely to be probed, both groups displayed a robust selection advantage for the flickering items. However, in the nonflicker-bias condition in which the nonflickering stimuli were likely to be probed, only healthy control subjects showed selection of the nonflickering items. Patients displayed a trend toward preferential memory for the flickering items, as in the unbiased condition. CONCLUSIONS Both groups were able to select salient over nonsalient stimuli, but patients with schizophrenia were unable to select nonsalient over salient stimuli, consistent with impairment in the effortful control of attention. These findings demonstrate the generality of top-down control failure in schizophrenia in the face of bottom-up competition from salient stimuli as with prepotent response tendencies.

Impaired response selection in schizophrenia: Evidence from the P3 wave and the lateralized readiness potential

Reaction times (RTs) are substantially prolonged in schizophrenia patients, but the latency of the P3 component is not. This suggests that the RT slowing arises from impairments in a late stage of processing. To test this hypothesis, 20 schizophrenia patients and 20 control subjects were tested in a visual oddball paradigm that was modified to allow measurement of the lateralized readiness potential (LRP), an index of stimulus-response translation processes. Difference waves were used to isolate the LRP and the P3 wave. Patients and control subjects exhibited virtually identical P3 difference waves, whereas the LRP difference wave was reduced in amplitude and delayed in latency in the patients. These results indicate that, at least in simple tasks, the delayed RTs observed in schizophrenia are primarily a consequence of impairments in the response selection and preparation processes that follow perception and categorization.

Toward the Neural Mechanisms of Reduced Working Memory Capacity in Schizophrenia

People with schizophrenia (PSZ) demonstrate reliable reductions in working memory (WM) capacity (i.e., the number of objects that can be held in memory). The present study asked whether WM impairments in PSZ can be explained by the same neural mechanisms that underlie individual differences in WM capacity among healthy individuals. Specifically, we examined event-related potentials in PSZ and healthy matched controls during a change detection task that required the storage of multiple objects in WM. The amplitude of contralateral delay activity (CDA), which correlates with WM capacity in healthy individuals, was larger in controls than in PSZ for memory loads of 3 and 5 objects, but larger in PSZ than in controls for a memory load of 1. This same pattern was found in the subgroups of PSZ and controls with an equivalent WM capacity. Moreover, the increase in CDA amplitude was correlated with individual differences in capacity in controls, but not in PSZ. These results demonstrate that WM impairment in PSZ is not associated with the same patterns of neural activity that characterize low WM capacity in healthy individuals. We propose that WM impairment in PSZ instead reflects a specific impairment in the ability to distribute attention broadly.

Mechanisms and Effects of Transcranial Direct Current Stimulation

The US Air Force Office of Scientific Research convened a meeting of researchers in the fields of neuroscience, psychology, engineering, and medicine to discuss most pressing issues facing ongoing research in the field of transcranial direct current stimulation (tDCS) and related techniques. In this study, we present opinions prepared by participants of the meeting, focusing on the most promising areas of research, immediate and future goals for the field, and the potential for hormesis theory to inform tDCS research. Scientific, medical, and ethical considerations support the ongoing testing of tDCS in healthy and clinical populations, provided best protocols are used to maximize safety. Notwithstanding the need for ongoing research, promising applications include enhancing vigilance/attention in healthy volunteers, which can accelerate training and support learning. Commonly, tDCS is used as an adjunct to training/rehabilitation tasks with the goal of leftward shift in the learning/treatment effect curves. Although trials are encouraging, elucidating the basic mechanisms of tDCS will accelerate validation and adoption. To this end, biomarkers (eg, clinical neuroimaging and findings from animal models) can support hypotheses linking neurobiological mechanisms and behavioral effects. Dosage can be optimized using computational models of current flow and understanding dose–response. Both biomarkers and dosimetry should guide individualized interventions with the goal of reducing variability. Insights from other applied energy domains, including ionizing radiation, transcranial magnetic stimulation, and low-level laser (light) therapy, can be prudently leveraged.