Lena H. Ernst

Differential prefrontal and frontotemporal oxygenation patterns during phonemic and semantic verbal fluency

Movement artifacts are still considered a problematic issue for imaging research on overt language production. This motion-sensitivity can be overcome by functional near-infrared spectroscopy (fNIRS). In the present study, 50 healthy subjects performed a combined phonemic and semantic overt verbal fluency task while frontal and temporal cortex oxygenation was recorded using multi-channel fNIRS. Results showed a partial dissociation for phonemic and semantic word generation with equally increased oxygenation in frontotemporal cortices for both types of tasks whereas anterior and superior prefrontal areas were exclusively activated during phonemic fluency. Also, a general left-lateralization was found being more pronounced during semantic processing. These findings line up with earlier imaging and lesion studies emphasizing a crucial role of the temporal lobe for semantic word production, whereas phonemic processing seems to depend on intact frontal lobe function.

Functional Amygdala-Hippocampus Connectivity During Anticipation of Aversive Events is Associated with Gray's Trait “Sensitivity to Punishment”

BACKGROUND The reinforcement sensitivity theory postulates a behavioral inhibition system that modulates reaction to stimuli indicating aversive events. Grays dimension of anxiety, reflecting human trait sensitivity to aversive events, determines the extent to which stimuli activate the behavioral inhibition system. Although structural brain imaging has previously identified the amygdala and the hippocampus as two major components related to the behavioral inhibition system, the functional dynamics of the responses in these structures remain unclear. METHODS In this study, we examined the event-related functional magnetic resonance imaging blood oxygen level-dependent response in the hippocampus and amygdala as well as the functional connectivity of the two regions during anticipation of monetary loss in 45 healthy human subjects. RESULTS Anticipation of loss elicited activation in the hippocampus as well as in the amygdala. Additionally, substantial functional connectivity between the two areas was observed. Furthermore, this functional connectivity was significantly correlated with individual differences in Grays trait sensitivity to aversive events. Specifically, higher trait sensitivity to aversive events was associated with increased functional connectivity following cues indicating potential loss. CONCLUSIONS In summary, we show that individual differences regarding Grays trait sensitivity to aversive events as defined by the reinforcement sensitivity theory are associated with the neural dynamics of the amygdala-hippocampal circuit during anticipation of aversive events. In particular, evidence is provided for a relationship between functional brain imaging data and a psychometric approach specifically measuring Grays trait sensitivity to aversive events, thereby potentially identifying the neural substrate of the behavioral inhibition system.

Inhibitory transcranial magnetic theta burst stimulation attenuates prefrontal cortex oxygenation

Recent studies highlighted the great potential of newly established theta burst stimulation (TBS) protocols for non‐invasive human brain stimulation studies using transcranial magnetic stimulation (TMS). While intermittent TBS over the primary motor cortex was found to potentiate motor evoked potentials, continuous TBS led to profound attenuations. Although numerous studies investigated the impact of TBS on motor cortex function, yet, only few imaging studies focused on its effects in other brain areas. Particularly for the prefrontal cortex, it is unclear whether TBS has similar effects compared to application over motor areas. In the current study continuous TBS was applied to either the left or right dorsolateral prefrontal cortex in a sample of healthy subjects. Changes in prefrontal oxygenation were measured during an emotional Stroop task by means of functional multi‐channel near‐infrared spectroscopy (fNIRS) before and after stimulation. Results showed bilaterally decreased prefrontal oxygenation following inhibitory stimulation of the left prefrontal cortex but no behavioral effect. No such alterations were observed following right‐hemispheric or sham stimulation. The results of the current study are in line with earlier findings and additionally demonstrate that also prefrontal oxygenation can be impaired by continuous TBS. Hum Brain Mapp, 2013.

Neural correlates of spontaneous panic attacks.

In this report, we present two anxiety disorder patients who spontaneously experienced a panic attack during an fMRI examination and subsequently aborted the measurement. We analyzed the functional data gathered up to that point in relation to the patients’ subsequent verbal reports of the course of the panic attacks. Within prominent structures of the fear network (amygdala, insula, prefrontal cortex) neural dynamics mirrored the description of the attack very well for one of the patients. For the other patient who experienced a less intense attack and who was treated pharmacologically at the time of measurement, the relation was limited to the prefrontal cortex. Investigating the temporal dynamics of neural activation in an ecologically valid situation may point to the potentially different roles of the amygdala and the insula as well as the prefrontal cortex prior to and during a panic attack.

Beyond the N400: complementary access to early neural correlates of novel metaphor comprehension using combined electrophysiological and haemodynamic measurements.

The simultaneous application of different neuroimaging methods combining high temporal and spatial resolution can uniquely contribute to current issues and open questions in the field of pragmatic language perception. In the present study, comprehension of novel metaphors was investigated using near-infrared spectroscopy (NIRS) combined with the simultaneous acquisition of electroencephalography (EEG)/event-related potentials (ERPs). For the first time, we investigated the effects of figurative language on early electrophysiological markers (P200, N400) and their functional relationship to cortical haemodynamic responses within the language network (Brocas area, Wernickes area). To this end, 20 healthy subjects judged 120 sentences with respect to their meaningfulness, whereby phrases were either literal, metaphoric, or meaningless. Our results indicated a metaphor-specific P200 reduction and a linear increase of N400 amplitudes from literal over metaphoric to meaningless sentences. Moreover, there were metaphor related effects on haemodynamic responses accessed with NIRS, especially within the left lateral frontal cortex (Brocas area). Significant correlations between electrophysiological and haemodynamic responses indicated that P200 reductions during metaphor comprehension were associated with an increased recruitment of neural activity within left Wernickes area, indicating a link between variations in neural activity and haemodynamic changes within Wernickes area. This link may reflect processes related to interindividual differences regarding the ability to classify novel metaphors. The present study underlines the usefulness of simultaneous NIRS measurements in language paradigms - especially for investigating the functional significance of neurophysiological markers that have so far been rarely examined - as these measurements are easily and efficiently realizable and allow for a complementary examination of neural activity and associated metabolic changes in cortical areas.

Functional near Infrared Spectroscopy in Psychiatry: A Critical Review

This review deals with the utilisation of functional near infrared (fNIR) spectroscopy for an in vivo assessment of activation changes in brain tissue, which has broadened the range of non-invasive functional imaging methods within the field of neuroscientific research. Due to its simple and quick applicability as well as the absence of side effects, fNIR spectroscopy is particularly well tolerated by psychiatric patients and can hence markedly contribute to the understanding of the neurobiological basis of psychiatric disorders. The optical, light-based method emits near infrared wavelengths of about 700–1000 nm, which are able to penetrate the scalp and skull, into the head. Because near infrared light is distinctively absorbed by the chromophores oxy-haemoglobin (O2Hb) and deoxy-haemoglobin (HHb), the measured relative amount of reflected NIR light can indicate regional oxygenation patterns in cortical brain tissue with a depth resolution of, on average, 1.5 cm and a spatial resolution of about 2–3 cm. Validity and reliability of fNIR spectroscopy measurements to assess task-related cognitive activation have been repeatedly confirmed among healthy subjects. Beyond that, the application of fNIR spectroscopy to detect altered cortical oxygenation in psychiatric patients during cognitive tasks has been greatly intensified over the last two decades. In this context, hypo-frontality, a decrease in frontal lobe activity that is associated with a number of clinical symptoms and psychiatric disorders, has been demonstrated in a wide range of fNIR spectroscopy studies with psychiatric patients. Despite its variety of beneficial properties, the most apparent disadvantages of NIR spectroscopy compared to other imaging techniques are its limited spatial as well as depth resolution and its restriction to cortical areas. Although multimodal approaches based on simultaneous application of NIR spectroscopy combined with other imaging techniques initially revealed promising results, further technical development and a broadened implementation of combined measurements are necessary in order to uncover distinct brain activity alterations in different psychiatric disorders. In addition to the need for further technical improvement of the method, broad and longitudinal applications of fNIR spectroscopy measurements in psychiatric research are required in order to identify robust diagnostic markers which are required to establish NIR spectroscopy as a valid inter-individual screening instrument in psychiatry.

Recovery of cortical functioning in abstinent alcohol-dependent patients: prefrontal brain oxygenation during verbal fluency at different phases during withdrawal.

Abstract Objectives. Neurotoxic effects of alcohol consumption are well-known. There is plenty of literature on frontal lobe impairment on the behavioural and structural brain imaging level. However, only few functional imaging studies investigated altered neural patterns and even less abstinence-related neural recovery. Methods. In a cross-sectional design three patient groups (acute withdrawal, detoxified, abstinent) and healthy controls (each n = 20) performed a phonological and semantic verbal fluency task (VFT) while brain activity was measured with near-infrared spectroscopy (NIRS). Results. First, for the phonological condition withdrawal patients and detoxified patients showed less fluency-related frontal lobe activation compared to controls despite equal performance. Second, significant linear trend effects from withdrawal patients over detoxified and abstinent patients up to healthy controls indicated more normal activation patterns in the abstinent group that did not differ significantly from the controls. In the detoxified group brain activation increased with time since detoxification. Conclusions. Our results are compatible with an increase in frontal brain activity from alcohol dependence over abstinence up to normal functioning. However, as cross-sectional designs do not allow to assess causal relations, results have to be considered preliminary and longitudinal studies are needed to further elucidate recovery processes in alcohol dependence.

N1 and N2 ERPs reflect the regulation of automatic approach tendencies to positive stimuli

The Approach-Avoidance Task (AAT) measures automatic approach-avoidance tendencies and their regulation: compatible reactions (approach positive, avoid negative) are faster than incompatible ones (approach negative, avoid positive). The present study assessed event-related potentials (ERPs) in 15 healthy persons for depicting neuropsychological sub-processes of such stimulus-response compatibility (SRC) effects. Early attention allocation preparing efficient stimulus classification (N1 ERP) and response inhibition on the level of response representations (N2 ERP) were found to underlie the solution of the AAT-conflict. For positive stimuli, these processes were enhanced during the incompatible condition avoid positive compared to the compatible condition approach positive. Source localization analysis revealed activity in right occipital areas (N1 ERP), and in left DLPFC and insula (N2 ERP) to be neuronal generators of these electrophysiological SRC effects. This neuronal regulation resulted in no influence of incompatibility at the behavioural level. For negative pictures, we found the reversed pattern: there were no electrophysiological SRC effects, but clear behavioural SRC effects in both RTs and error frequency, i.e. participants were faster and made fewer errors during avoiding than approaching negative pictures. These valence-specific differences are in line with previous studies indicating negative stimuli - probably due to higher importance for survival - to more strongly influence behaviour.

Controlled attention allocation mediates the relation between goal-oriented pursuit and approach–avoidance reactions to negative stimuli

Approach and avoidance are two basic behavioural principles. The current study investigated neuropsychological mechanisms underlying the influence of the personality characteristic goal-oriented pursuit on the efficiency of regulating such approach-avoidance reactions. Therefore, the P3 event-related potential (ERP) reflecting controlled attention allocation was assessed during the Approach-Avoidance Task (AAT) with positive and negative pictures in 36 healthy participants. For negative pictures, analyses revealed the neuropsychological mechanism of controlled attention allocation to mediate the relation between personality and behaviour: Stronger goal-oriented pursuit was associated with higher controlled attention allocation to the incompatible compared to the compatible condition and--thereby--with less automatic avoidance tendencies in response to negative pictures, i.e., with higher efficiency of regulation. Results are discussed in terms of their implications for future studies on mechanisms determining the influence of personality traits, situational factors and their interaction on approach-avoidance behaviour.

Quetiapine and flupentixol differentially improve anterior cingulate cortex function in schizophrenia patients: an event-related potential study

Atypical antipsychotic agents are a frequently and effectively used treatment in schizophrenia and psychotic disorders. Other than conventional antipsychotics, which mainly exert their pharmacological effect in subcortical dopaminergic systems, atypical antipsychotics additionally affect partly serotonergically innervated structures within prefrontal areas, such as the anterior cingulate cortex (ACC). However, only few controlled, randomized studies have so far investigated direct and indirect effects of atypical antipsychotics on the ACC and, up until now, no clinical investigation has exclusively addressed the specific effects of quetiapine on ACC function. The present study assessed ACC function in 18 quetiapine-medicated patients and 13 flupentixol-treated patients suffering from schizophrenia by means of the error-related negativity (ERN), a neurophysiological marker of ACC function, in a pre-post design. Between-group comparisons revealed different effects of quetiapine and flupentixol on ACC function despite similar improvement in psychopathology, cognitive performance and quality of life. Whereas atypical treatment was associated with an increase in amplitudes over time, there were prolonged ERN peak latencies in patients treated with the typical agent. Moreover, treatment effects depended on baseline prefrontal cortex function in both groups. We conclude that both flupentixol and quetiapine improve prefrontal function especially in patients with weak initial ACC function which might be due to their shared affinity for serotonin receptors in frontal brain regions. However, since this affinity is more pronounced for quetiapine, patients treated with quetiapine seemed to profit more evidently concerning their prefrontal cortex function compared to patients of the flupentixol group, who exhibited a compensatory prolongation of processes.