Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study.

The safety and efficacy of neuronavigated intermittent theta burst stimulation (iTBS) in patients with bipolar depression has not yet been investigated. We hypothesized the superiority of active iTBS over sham. Twenty-six patients were randomly allocated to receive either active (n=12) or sham (n=14) iTBS. Response and remission rates according to changes in depression MADRS score were high following active iTBS (72% and 42% for response and remission rates, respectively), but no significant difference was found after sham stimulation (42%and 25%). No adverse events were observed. This study revealed the safety and tolerability of twice daily iTBS in patients with bipolar depression. Larger controlled studies are warranted to prove iTBS superiority in treatment-resistant bipolar depression.

Mapping dynamical properties of cortical microcircuits using robotized TMS and EEG: Towards functional cytoarchitectonics.

Brain dynamics at rest depend on the large-scale interactions between oscillating cortical microcircuits arranged into macrocolumns. Cytoarchitectonic studies have shown that the structure of those microcircuits differs between cortical regions, but very little is known about interregional differences of their intrinsic dynamics at a macro-scale in human. We developed here a new method aiming at mapping the dynamical properties of cortical microcircuits non-invasively using the coupling between robotized transcranial magnetic stimulation and electroencephalography. We recorded the responses evoked by the stimulation of 18 cortical targets largely covering the accessible neocortex in 22 healthy volunteers. Specific data processing methods were developed to map the local source activity of each cortical target, which showed inter-regional differences with very good interhemispheric reproducibility. Functional signatures of cortical microcircuits were further studied using spatio-temporal decomposition of local source activities in order to highlight principal brain modes. The identified brain modes revealed that cortical areas with similar intrinsic dynamical properties could be distributed either locally or not, with a spatial signature that was somewhat reminiscent of resting state networks. Our results provide the proof of concept of "functional cytoarchitectonics", that would guide the parcellation of the human cortex using not only its cytoarchitecture but also its intrinsic responses to local perturbations. This opens new avenues for brain modelling and physiopathology readouts.

Is the impairment in temporal allocation of visual attention in children with ADHD related to a developmental delay or a structural cognitive deficit?

We investigated the temporal allocation of visual attention in 11-year-old children with attention-deficit/hyperactivity disorder (ADHD) by comparing their attentional blink (AB) parameters (duration, amplitude and minimum performance) with those observed in three groups of healthy control participants (8-year-olds, 11-year-olds and adults). The AB is a marker of impaired ability to detect a second target following the identification of a first target when both appear randomly within a rapid sequence of distractor items. Our results showed developmental effects; with age, the AB duration decreased and the AB minimum moved to shorter lag times. Importantly, 11-year old children with ADHD presented much the same similar AB patterns (in terms of duration and minimum position) as the healthy 8-year-old controls. Our results support the hypothesis whereby impaired allocation of temporal selective attention in children with ADHD is due to a developmental delay and not a specific cognitive deficit.

What saccadic eye movements tell us about TMS-induced neuromodulation of the DLPFC and mood changes: a pilot study in bipolar disorders.

The study assumed that the antisaccade (AS) task is a relevant psychophysical tool to assess (i) short-term neuromodulation of the dorsolateral prefrontal cortex (DLPFC) induced by intermittent theta burst stimulation (iTBS); and (ii) mood change occurring during the course of the treatment. Saccadic inhibition is known to strongly involve the DLPFC, whose neuromodulation with iTBS requires less stimulation time and lower stimulation intensity, as well as results in longer aftereffects than the conventional repetitive transcranial magnetic stimulation (rTMS). Active or sham iTBS was applied every day for 3 weeks over the left DLPFC of 12 drug-resistant bipolar depressed patients. To assess the iTBS-induced short-term neuromodulation, the saccadic task was performed just before (S1) and just after (S2) the iTBS session, the first day of each week. Mood was evaluated through Montgomery and Asberg Depression Rating Scale (MADRS) scores and the difference in scores between the beginning and the end of treatment was correlated with AS performance change between these two periods. As expected, only patients from the active group improved their performance from S1 to S2 and mood improvement was significantly correlated with AS performance improvement. In addition, the AS task also discriminated depressive bipolar patients from healthy control subjects. Therefore, the AS task could be a relevant and useful tool for clinicians to assess if the Transcranial magnetic stimulation (TMS)-induced short-term neuromodulation of the DLPFC occurs as well as a "trait vs. state" objective marker of depressive mood disorder.

Age-related changes in intracortical inhibition are mental-cognitive state-dependent.

INTRODUCTION: This study aimed to assess the impact of aging and 'state-dependency' on cortical excitability. Two studies investigated these factors using a motor task and found that the age-related differences observed at rest disappeared in the task condition. However, as both their tasks and excitability measurements involved the motor cortex, their results could be specific only to the motor system. To overcome this problem, the present study used a cognitive task to control mental state. METHOD: Intracortical inhibition/facilitation (ICI/ICF) were assessed in young and older adults at rest and during the cognitive task. The cortical silent period (CSP) was also evaluated. RESULTS: ICI and CSP were reduced with aging. However, ICI differences between young and old people disappeared when they performed the cognitive task. CONCLUSION: Age and mental state modify cortical excitability. Taking these factors into consideration is crucial to clinical research using cortical excitability as a possible biomarker of pathology.

Antisaccades as a follow-up tool in major depressive disorder therapies: a pilot study.

Eight patients with major depression, included in a double-blind study, performed an antisaccade task. Results suggested a link between antisaccade performances and clinical scale scores in patients who respond to therapy. Moreover, error rates may well predict response from day of inclusion, thus serving as a state-marker for mood disorders.

Saccadic performance and cortical excitability as trait-markers and state-markers in rapid cycling bipolar disorder: a two-case follow-up study.

BACKGROUND: The understanding of physiopathology and cognitive impairments in mood disorders requires finding objective markers. Mood disorders have often been linked to hypometabolism in the prefrontal dorsolateral cortex, and to GABAergic and glutamatergic neurotransmission dysfunction. The present study aimed to discover whether saccadic tasks (involving DPLFC activity), and cortical excitability (involving GABA/Glutamate neurotransmission) could provide neuropsychophysical markers for mood disorders, and/or of its phases, in patients with rapid cycling bipolar disorders (rcBD). METHODS: Two rcBD patients were followed for a cycle, and were compared to nine healthy controls. A saccade task, mixing prosaccades, antisaccades, and nosaccades, and an evaluation of cortical excitability using transcranial magnetic stimulation were performed. RESULTS: We observed a deficit in antisaccade in patients independently of thymic phase, and in nosaccade in the manic phase only. Cortical excitability data revealed global intracortical deficits in all phases, switching according to cerebral hemisphere and thymic phase. CONCLUSION: Specific patterns of performance in saccade tasks and cortical excitability could characterize mood disorders (trait-markers) and its phases (state-markers). Moreover, a functional relationship between oculometric performance and cortical excitability is discussed.

Having to identify a target reduces antisaccade latencies in mixed saccadic paradigms: A top-down effect released by tonic prefrontal activation?

Instructing participants to "identify a target" dramatically reduces saccadic reaction times in prosaccade tasks (PS). However, it has been recently shown that this effect disappears in antisaccade tasks (AS). The instruction effect observed in PS may result from top-down processes, mediated by pathways connecting the prefrontal cortex (PFC) to the superior colliculus. In AS, the PFC's prior involvement is in competition with the instruction process, annulling its effect. This study aims to discover whether the instruction effect persists in mixed paradigms. According to Dyckman's fMRI study (2007), the difficulty of mixed tasks leads to PFC involvement. The antisaccade-related PFC activation observed on comparison of blocked AS and PS therefore disappears when the two are compared in mixed paradigms. However, we continued to observe the instruction effect for both PS and AS. We therefore posit different types of PFC activation: phasic during blocked AS, and tonic during mixed saccadic experiments.

Visual demand and visual field presentation influence natural scene processing.

BACKGROUND: Bottom-up and top-down processes are involved in visual analysis of scenes. Here we examined the influence of top-down visual demand on natural scene processing. METHODS: We measured accuracy and response time in adults performing two stimuli-equivalent tasks. Unfiltered, low or high spatial frequency (SF) natural scenes were presented in central, left, or right visual fields (CVF, LVF, RVF). The tasks differed only by the instructed visual demand. In the detection task, participants had to decide whether a scene was present or not. In the categorization task, they had to decide whether the scene was a city or a forest. RESULTS: Higher accuracy was seen for the LVF in the detection task, but for categorization, greater accuracy was seen for the RVF. The interaction between Task and SF revealed coarse-to-fine processing in the categorization task for both accuracy and reaction time, which nearly disappeared in the detection task. Considering the interaction of Task, VF and SF, a left-hemisphere specialisation (i.e., RVF advantage) was observed for the categorisation of HSF scenes for accuracy alone, whereas a LVF advantage was seen for all SFs in the detection task for both accuracy and reaction time. CONCLUSION: Our results revealed that the nature of top-down visual demand is essential to understanding how visual analysis is achieved in each hemisphere. Moreover, this study examining the effects of visual demand, visual field presentation, and SF content of stimuli through the use of ecological stimuli provides a tool to enrich the clinical examination of visual and neurovisual patients.

The neural substrates and timing of top-down processes during coarse-to-fine categorization of visual scenes: a combined fMRI and ERP study.

Spatial frequencies in an image influence visual analysis across a distributed, hierarchically organized brain network. Low spatial frequency (LSF) information may rapidly reach high-order areas to allow an initial coarse parsing of the visual scene, which could then be "retroinjected" through feedback into lower level visual areas to guide finer analysis on the basis of high spatial frequency (HSF). To test this "coarse-to-fine" processing scheme and to identify its neural substrates in the human brain, we presented sequences of two spatial-frequency-filtered scenes in rapid succession (LSF followed by HSF or vice versa) during fMRI and ERPs in the same participants. We show that for low-to-high sequences (but not for high-to-low sequences), LSF produces a first increase of activity in prefrontal and temporo-parietal areas, followed by enhanced responses to HSF in primary visual cortex. This pattern is consistent with retroactive influences on low-level areas that process HSF after initial activation of higher order areas by LSF.

Specific impairments in visual processing following lesion side in hemianopic patients.

INTRODUCTION: Following unilateral damage of the primary visual cortex one of the most common visual field defects observed is Homonymous Hemianopia (HH), a loss of vision of the contralesional hemifield in each eye. The ipsilesional ("intact") part of the central visual field is often used to compensate for difficulties encountered in the peripheral hemianopic visual field. However, the quality of vision within the central visual field is not well-known. METHODS: To better describe and understand visual processing in hemianopia, two tasks were conducted with 25 healthy controls, six left hemianopes, and five right hemianopes. Filtered (in high, above 6 cycles/degree, or low, below 4 cycles/degree, spatial frequencies - HSF and LSF, respectively) and unfiltered natural scene images (5° of visual angle) were briefly presented (100 msec) centrally on a computer screen. Participants were required either to respond when a natural scene was presented (yes/no detection task) or to indicate if the stimulus was a city or a highway (categorization task). RESULTS: The three groups showed similar accuracy levels but significant differences were observed in response times. More precisely, left hemianopes were impaired both in the detection and in the categorization tasks whereas right hemianopes were only impaired in the categorization task. However, the three groups had similar responses to spatial frequencies: HSF were processed more slowly than LSF. CONCLUSIONS: Overall these results suggest that central vision is not intact in hemianopia. Lesion side selectively affects reaction times (RTs) in the detection and the categorization tasks, but does not seem to determine a specific deficit in spatial frequency processing.

Having to identify a target reduces latencies in prosaccades but not in antisaccades.

In a princeps study, Trottier and Pratt (2005) showed that saccadic latencies were dramatically reduced when subjects were instructed to not simply look at a peripheral target (reflexive saccade) but to identify some of its properties. According to the authors, the shortening of saccadic reactions times may arise from a top-down disinhibition of the superior colliculus (SC), potentially mediated by the direct pathway connecting frontal/prefrontal cortex structures to the SC. Using a "cue paradigm" (a cue preceded the appearance of the target), the present study tests if the task instruction (Identify vs. Glance) also reduces the latencies of antisaccades (AS), which involve prefrontal structures. We show that instruction reduces latencies for prosaccade but not for AS. An AS requires two processes: the inhibition of a reflexive saccade and the generation of a voluntary saccade. To separate these processes and to better understand the task effect we also test the effect of the task instruction only on voluntary saccades. The effect still exists but it is much weaker than for reflexive saccades. The instruction effect closely depends on task demands in executive resources.

Can headway reduction in fog be explained by impaired perception of relative motion?

OBJECTIVE: The goal of this study was to provide a better understanding of driver behavior in fog. BACKGROUND: Impaired perception of changes in headway is hypothesized to be one of the reasons for shorter following distances in foggy conditions as compared with clear weather. METHOD: In the experiments described here, we measured response time for discriminating between whether the vehicle ahead is getting closer or farther away. Several visibility conditions were studied, ranging from a no-fog condition to a condition in which the vehicle could be seen only by its rear fog lights. RESULTS: Fog conditions increased response times when the outline of the vehicle was barely visible or not visible at all. The longer response times in fog were attributable to the low contrast of the vehicle outline when still visible and to the smaller spacing between the two lights when the outline could not be properly perceived. Moreover, response times were found to be shorter for shorter following distances and for faster accelerations. CONCLUSION: Reducing headway could be a way for drivers to achieve faster discrimination of relative motion in foggy weather. More specifically, shortening one's following distance until visibility of the lead vehicle changes from bad to good may have a perceptual control benefit, insofar as the response time gain compensates for the reduction in headway under these conditions. APPLICATIONS: Potential applications include improving traffic safety. The results provide a possible explanation for close following in fog and point out the importance of rear-light design under these conditions.

Effect of temporal constraints on hemispheric asymmetries during spatial frequency processing.

Studies on functional hemispheric asymmetries have suggested that the right vs. left hemisphere should be predominantly involved in low vs. high spatial frequency (SF) analysis, respectively. By manipulating exposure duration of filtered natural scene images, we examined whether the temporal characteristics of SF analysis (i.e., the temporal precedence of low on high spatial frequencies) may interfere with hemispheric specialization. Results showed the classical hemispheric specialization pattern for brief exposure duration and a trend to a right hemisphere advantage irrespective of the SF content for longer exposure duration. The present study suggests that the hemispheric specialization pattern for visual information processing should be considered as a dynamic system, wherein the superiority of one hemisphere over the other could change according to the level of temporal constraints: the higher the temporal constraints of the task, the more the hemispheres are specialized in SF processing.

Neural correlates of spatial frequency processing: A neuropsychological approach.

We examined the neural correlates of spatial frequency (SF) processing through a gender and neuropsychological approach, using a recognition task of filtered (either in low spatial frequencies/LSF or high spatial frequencies/HSF) natural scene images. Experiment 1 provides evidence for hemispheric specialization in SF processing in men (the right hemisphere is predominantly involved in LSF analysis and the left in HSF analysis) but not in women. Experiment 2 aims to investigate the role of the right occipito-temporal cortex in LSF processing with a neurological female patient who had a focal lesion of this region due to an embolization of an arterioveinous malformation. This study was conducted 1 week before and 6 months after the surgical intervention. As expected, after the embolization, LSF scene recognition was more impaired than HSF scene recognition. These data support the hypothesis that the right occipito-temporal cortex might be preferentially specialized for LSF information processing and more generally suggest a hemispheric specialization in SF processing in females, although it is difficult to demonstrate in healthy women.

Visual search for object orientation can be modulated by canonical orientation.

The authors studied the influence of canonical orientation on visual search for object orientation. Displays consisted of pictures of animals whose axis of elongation was either vertical or tilted in their canonical orientation. Target orientation could be either congruent or incongruent with the object's canonical orientation. In Experiment 1, vertical canonical targets were detected faster when they were tilted (incongruent) than when they were vertical (congruent). This search asymmetry was reversed for tilted canonical targets. The effect of canonical orientation was partially preserved when objects were high-pass filtered, but it was eliminated when they were low-pass filtered, rendering them as unfamiliar shapes (Experiment 2). The effect of canonical orientation was also eliminated by inverting the objects (Experiment 3) and in a patient with visual agnosia (Experiment 4). These results indicate that orientation search with familiar objects can be modulated by canonical orientation, and they indicate a top-down influence on orientation processing.

Cerebral regions and hemispheric specialization for processing spatial frequencies during natural scene recognition. An event-related fMRI study.

It has been suggested that visual scene recognition is mainly based on spatial frequency (Fourier) analysis of the image. This analysis starts with processing low spatial frequencies (LSF), followed by processing high spatial frequencies (HSF). Within the framework of the spatial frequency analysis, the right/left hemisphere would be predominantly involved in LSF/HSF analysis, respectively. The aim of this event-related fMRI study was to evaluate neural correlates and hemispheric specialization of spatial frequency analysis during recognition of nonfiltered (NF) and filtered, either in LSF or HSF, natural scenes. Comparing LSF or NF to HSF scene recognition, significant activation was obtained within right anterior temporal cortex and right parahippocampal gyrus. As these regions are known to be involved in scene processing, we interpret this result as suggesting that scene recognition is mainly based on LSF extraction and analysis. When LSF scene was compared to HSF scene recognition, supplementary activation was obtained within the right inferior parietal lobule that likely reflects attentional modulation on spatial frequency processing. A direct interhemispheric comparison for each particular band of spatial frequencies highlighted predominance within the early visual areas (such as the middle occipital gyrus) to the right for LSF processing and to the left for HSF processing. This result provides supplementary evidence for hemispheric specialization at early levels of visual analysis when spatial frequencies are processed.

Image phase or amplitude? Rapid scene categorization is an amplitude-based process.

Models of the visual cortex are based on image decomposition according to the Fourier spectrum (amplitude and phase). On one hand, it is commonly believed that phase information is necessary to identify a scene. On the other hand, it is known that complex cells of the visual cortex, the most numerous ones, code only the amplitude spectrum. This raises the question of knowing if these cells carry sufficient information to allow visual scene categorization. In this work, using the same experiments in computer simulation and in psychophysics, we provide arguments to show that the amplitude spectrum alone is sufficient for categorization task.

Hemispheric specialization for spatial frequency processing in the analysis of natural scenes.

Experimental data coming from visual cognitive sciences suggest that visual analysis starts with a parallel extraction of different visual attributes at different scales/frequencies. Neuropsychological and functional imagery data have suggested that each hemisphere (at the level of temporo-parietal junctions-TPJ) could play a key role in spatial frequency processing: The right TPJ should predominantly be involved in low spatial frequency (LFs) analysis and the left TPJ in high spatial frequency (HFs) analysis. Nevertheless, this functional hypothesis had been inferred from data obtained when using the hierarchical form paradigm, without any explicit spatial frequency manipulation per se. The aims of this research are (i) to investigate, in healthy subjects, the hemispheric asymmetry hypothesis with an explicit manipulation of spatial frequencies of natural scenes and (ii) to examine whether the 'precedence effect' (the relative rapidity of LFs and HFs processing) depends on the visual field of scene presentation or not. For this purpose, participants were to identify either non-filtered or LFs and HFs filtered target scene displayed either in the left, central, or right visual field. Results showed a hemispheric specialization for spatial frequency processing and different 'precedence effects' depending on the visual field of presentation.