Daniela Mannarelli

Prefrontocerebellar transcranial direct current stimulation increases amplitude and decreases latency of P3b component in patients with euthymic bipolar disorder

Introduction Neurocognitive impairments have been observed in patients with bipolar disorder (BD) even during the euthymic phase of the disease, potentially representing trait-associated rather than state-associated characteristics of the disorder. In the present study, we used transcranial direct current stimulation (tDCS) applied to cerebellar and prefrontal cortices to improve the neurophysiological performances of patients with euthymic BD. Methods Twenty-five outpatients with BD underwent open-label prefrontocerebellar tDCS for 3 consecutive weeks. Neurophysiological performances were assessed through the examination of the P3b and P3a subcomponents of P300 event-related potential at baseline and after stimulation. Results Compared to baseline, P3b component after tDCS showed significantly higher amplitude and shorter latency (latency: Fz P=0.02, Cz P=0.03, and Pz P=0.04; amplitude: Fz P=0.24, Cz P=0.02, and Pz P=0.35). Conclusion In our sample of patients with euthymic BD, concomitant prefrontoexcitatory and cerebellar-inhibitory modulations led to improved brain information processing stream. This improvement may at least partially result from neuroplastic modulation of prefrontocerebellar circuitry activity.

The Role of the Right Dorsolateral Prefrontal Cortex in Phasic Alertness: Evidence from a Contingent Negative Variation and Repetitive Transcranial Magnetic Stimulation Study

Phasic alertness represents the ability to increase response readiness to a target following an external warning stimulus. Specific networks in the frontal and parietal regions appear to be involved in the alert state. In this study, we examined the role of the right dorsolateral prefrontal cortex (DLPFC) during the attentional processing of a stimulus using a cued double-choice reaction time task. The evaluation of these processes was conducted by means of Event-Related Potentials (ERPs), in particular by using the Contingent Negative Variation (CNV), and repetitive 1-Hz Transcranial Magnetic Stimulation (rTMS). Transient virtual inhibition of the right DLPFC induced by real 1-Hz rTMS stimulation led to a significant decrease in total CNV and W1-CNV areas if compared with the basal and post-sham rTMS conditions. Reaction times (RTs) did not decrease after inhibitory rTMS, but they did improve after sham stimulation. These results suggest that the right DLPFC plays a crucial role in the genesis and maintenance of the alerting state and learning processes.

Attentional processing in bulbar- and spinal-onset amyotrophic lateral sclerosis: Insights from event-related potentials

Abstract Our objective was to evaluate attentional processing with respect to the clinical-onset subtype in amyotrophic lateral sclerosis (ALS) using event-related potentials (ERPs). Thirty-three non-demented ALS patients (22 spinal onset, 11 bulbar onset) and 32 age- and gender-matched controls underwent a psychophysiological evaluation. Mismatch Negativity (MMN), P300 components and Contingent Negative Variation (CNV) were obtained. Latencies and amplitudes of the MMN, P3a and P3b waves and CNV amplitude were then evaluated. Clinical parameters were correlated with ERP data. No differences emerged between ALS patients and controls with regard to the MMN and P3b components. N1-P3a inter-peak latency (Fz, p = 0.003; Cz, p = 0.001; Pz, p = 0.002) was longer in ALS-b than in ALS-s. Total CNV area (Cz, p = 0.01) and W1-CNV area were significantly reduced (Cz, p = 0.05; Pz, p = 0.03) in ALS-b with respect to the one of the controls, while no differences were found between ALS-s patients and controls. In conclusion, automatic pre-attentive processing of stimuli seems to be preserved in ALS. However, a significant delay in the time-course of selective attentive processing and a difficulty in initiating and sustaining attention may be present in ALS-b, which points to a possible dysfunction in the frontal neural network that responds to novelty and to abnormal integration of associative functions. This attentional impairment should be taken in account while developing alternative communicative strategies in ALS patients.

Unusual posterior reversible encephalopathy syndrome in a case of influenza A/H1N1 infection

Central nervous system involvement is an uncommon though potentially a severe complication during influenza infection; the pathogenic mechanisms of the neurological syndromes described in humans are largely unknown. We describe a case of a 51-year-old man who presented with fever and behavioral changes but no focal neurological deficits. The next day, the condition rapidly evolved into a severe neurological syndrome with recurrent focal motor seizures with secondary generalization. At the brain MRI, FLAIR disclosed a slight area of increased signal in the left mesial frontal cortex extending to the frontopolar area and insula. At DWI, a mild hyperintensity was evident in the mesial-frontopolar cortex, with normal ADC values. MR perfusion was indicative of severe hypoperfusion. Fungal, bacterial and viral cultures in CSF, blood and urine were negative. The nasopharyngeal swab PCR was positive for the H1N1-influenza A virus. The patient was thus treated and by day five the neurological examination results had returned to normal. A follow-up MRI, performed two weeks later, only revealed a residual slight hyperintensity in the left medial frontal cortex. The onset of a rapidly evolving encephalopathy syndrome, its close association with a MRI brain pattern of acute vasogenic edema and favorable outcome support a diagnosis of PRES during influenza A infection. However, the topographic characteristics of the cerebral lesion seem to define a PRES with an atypical pattern.

Effects of cerebellar transcranial direct current stimulation on attentional processing of the stimulus: Evidence from an event-related potentials study

Attentional processing consists of a set of processes that manage the flow of information through the nervous system and appropriately allocate attentional resources to relevant stimuli. Specific networks in the frontal and parietal regions appear to be involved in attention. The cerebellum has been identified as a subcortical structure that interacts with cortical brain areas, thereby controlling attentional processes. The aim of this study was to investigate the role of the cerebellum in attentional processing of the stimulus using a P300 Novelty task. We studied the effects of transcranial Direct Current Stimulation (tDCS) delivered over the left cerebellar hemisphere in cathodal, anodal and sham sessions on the P300 components in healthy subjects. Only cathodal cerebellar tDCS significantly reduced the amplitude of the N1, N2 and P3 components for both the target and novel stimuli. Moreover, N1 latency for all the stimuli was shorter after the cathodal tDCS session than after the sham or anodal sessions. These results point to a role of the cerebellum in attentional processing of the stimulus. The cerebellum may act indirectly by regulating and managing the activation and inhibition levels of the cortical areas involved in attentional networks.

Prefronto-cerebellar tDCS enhances neurocognition in euthymic bipolar patients. Findings from a placebo-controlled neuropsychological and psychophysiological investigation

OBJECTIVES The present double blind placebo-controlled study aimed at investigating the efficacy of 3-weeks prefronto-cerebellar transcranial direct current stimulation (tDCS) on neurocognitive functioning in euthymic BD patients. METHODS Forty-two outpatients with BD were randomly assigned to receive either active (n=21) or sham (n=21) prefronto-cerebellar tDCS for 3 consecutive weeks. Neurocognitive abilities were assessed with both neuropsychological testing and psychophysiological evaluation with a P300 novelty task. RESULTS Our results showed that (i) Trail Making Test-B, a measure of executive functioning, decreased significantly in the active but not in the sham group, (ii) Rey Complex Figure Test Delay Recall, a measure of visuospatial memory, increased significantly in both groups with a greater increase in the active compared to the sham group, and (iii) P3b latency, a measure of brain information processing stream, decreased significantly in the active but not in the sham group. No significant changes were observed in the other explored neuropsychological and psychophysiological measures. CONCLUSIONS The study suggests that concomitant prefrontal-excitatory and cerebellar-inhibitory tDCS in euthymic BD patients may lead to better neurocognitive performance, quantified through neuropsychological and psychophysiological measures.

P300 component in euthymic patients with bipolar disorder type I, bipolar disorder type II and healthy controls: A preliminary event-related potential study

The aim of the present study was to investigate P300 event-related potential components in euthymic bipolar disorder type I (BDI) and bipolar disorder type II (BDII) patients and matched controls. A total of 10 BDI patients, 10 BDII patients and 10 healthy individuals were enrolled in the study. Event-related potential data were collected according to a standard auditory ‘oddball’ paradigm. A significant groups effect in both the peak amplitude (P<0.001) and the mean amplitude (P<0.001) was observed; post-hoc comparisons showed that the peak and mean amplitudes of BDI and BDII patients were significantly lower than the peak and mean amplitudes of the healthy controls. The neurophysiological patterns found in the present study might at least partially reflect the presence of a mild selective cognitive impairment in euthymic BDI and BDII patients. From a clinical point of view, these evidences support the potential role of cognitive interventions in the treatment of BD.

Phasic alertness in a cued double-choice reaction time task: A Contingent Negative Variation (CNV) study

A phasic change in alertness is produced every time that a warning stimulus precedes a target, and it enhances and maintains the response readiness to an impending stimulus. In the present study, we investigated the Contingent Negative Variation (CNV) phenomenon, as index of phasic alertness, during a S1-S2 paradigm in which the imperative stimulus was represented by a double-choice reaction time task, designed to increase the executive requests at S2. Subjects performed the task at three consecutive time points in order to explore the CNV activity over time. The repetition of a cued double-choice reaction time task reduced the reaction times (RTs), while CNV amplitude remained steady along the sessions. Our data suggest that the continuous recruitment of attentional resources does not undergo habituation when it is related to the brain activity required in the maintenance of working memory when the mental model of the stimulus environment is updated.

An electrophysiological approach to tinnitus interpretation

INTRODUCTION Serotonin seems to play a central role in tinnitus. The intensity dependence of auditory evoked potential (IDAP) is considered an index of central serotonergic activity in the auditory cortex. The higher the steepness of the N1/P2 component amplitude-stimulus function slope (N1/P2 ASF slope as calculated by IDAP), the lower the central serotonergic activity. Similarly, the N1 amplitude-stimulus function slope (N1 ASF slope) was investigated. Auditory brainstem responses (ABR) examine the auditory system functionality from the periphery and through the brainstem, where serotonergic projections have been identified. OBJECTIVES Assessing whether tinnitus perception neurotransmitters activity inbalance could be investigated by an electrophysiological approach. MATERIALS AND METHODS Ten normoacousic tinnitus patients and 14 healthy controls were included in the study. Subjects underwent EEG (IDAP) recording, ABR recording and psychometric questionnaires administration. RESULTS N1/P2 ASF slope and N1ASF slope tended to have a greater steepness in patients. N1ASF slope was significantly correlated with ABR wave V and interpeak III-V latencies in patients. ABR wave V and interpeak III-V latencies were significantly longer in patients than in controls. CONCLUSION N1/P2 ASF slope, N1 ASF slope and ABR components appear to be useful electrophysiologic methods to study possible functional alterations related to the serotonergic activity.

Selective attentional impairment in chronic tinnitus: Evidence from an event-related potentials study

OBJECTIVE Tinnitus is an auditory phantom sensation experienced in the absence of a sound source. Cognitive dysfunctions, especially in working memory and attention, are frequently reported to be associated with tinnitus. The aim of this study was to investigate attentional functioning in a group of subjects with chronic tinnitus using ERPs, and in particular the P300 components. METHODS We studied 20 patients with chronic tinnitus and 20 healthy subjects that performed a P300 Novelty task. RESULTS P3a amplitude was significantly lower in tinnitus subjects than in controls. P3a latency was comparable in patients and controls. The P3b parameters were similar in the two groups. N1 latency for all the stimuli was significantly longer in tinnitus subjects than in controls. CONCLUSION These results point to a general slowing in early stimulus perception in tinnitus subjects. Moreover, a specific difficulty emerged in attentional switching to unexpected events during an orienting response, probably owing to a dysfunction in the ventral attention network. SIGNIFICANCE Psychophysiological approach reveals selective attentional impairment and could provide useful data for rehabilitative strategies in chronic tinnitus.