Effects of Rhythmic Transcranial Magnetic Stimulation in the Alpha-Band on Visual Perception Depend on Deviation From Alpha-Peak Frequency: Faster Relative Transcranial Magnetic Stimulation Alpha-Pace Improves Performance.

Alpha-band oscillatory activity over occipito-parietal areas is involved in shaping perceptual and cognitive processes, with a growing body of electroencephalographic (EEG) evidence indicating that pre-stimulus alpha-band amplitude relates to the subjective perceptual experience, but not to objective measures of visual task performance (discrimination accuracy). The primary aim of the present transcranial magnetic stimulation (TMS) study was to investigate whether causality can be established for this relationship, using rhythmic (alpha-band) TMS entrainment protocols. It was anticipated that pre-stimulus 10 Hz-TMS would induce changes in subjective awareness ratings but not accuracy, in the visual hemifield contralateral to TMS. To test this, we administered 10 Hz-TMS over the right intraparietal sulcus prior to visual stimulus presentation in 17 participants, while measuring their objective performance and subjective awareness in a visual discrimination task. Arrhythmic and 10 Hz sham-TMS served as control conditions (within-participant design). Resting EEG was used to record individual alpha frequency (IAF). A study conducted in parallel to ours with a similar design but reported after we completed data collection informed further, secondary analyses for a causal relationship between pre-stimulus alpha-frequency and discrimination accuracy. This was explored through a regression analysis between rhythmic-TMS alpha-pace relative to IAF and performance measures. Our results revealed that contrary to our primary expectation, pre-stimulus 10 Hz-TMS did not affect subjective measures of performance, nor accuracy, relative to control-TMS. This null result is in accord with a recent finding showing that for influencing subjective measures of performance, alpha-TMS needs to be applied post-stimulus. In addition, our secondary analysis showed that IAF was positively correlated with task accuracy across participants, and that 10 Hz-TMS effects on accuracy-but not awareness ratings-depended on IAF: The slower (or faster) the IAF, relative to the fixed 10 Hz TMS frequency, the stronger the TMS-induced performance improvement (or worsening), indicating that 10 Hz-TMS produced a gain (or a loss) in individual performance, directly depending on TMS-pace relative to IAF. In support of recent reports, this is evidence for alpha-frequency playing a causal role in perceptual sensitivity likely through regulating the speed of sensory sampling.

Parietal alpha tACS shows inconsistent effects on visuospatial attention.

Transcranial alternating current stimulation (tACS) is a popular technique that has been used for manipulating brain oscillations and inferring causality regarding the brain-behaviour relationship. Although it is a promising tool, the variability of tACS results has raised questions regarding the robustness and reproducibility of its effects. Building on recent research using tACS to modulate visuospatial attention, we here attempted to replicate findings of lateralized parietal tACS at alpha frequency to induce a change in attention bias away from the contra- towards the ipsilateral visual hemifield. 40 healthy participants underwent tACS in two separate sessions where either 10 Hz tACS or sham was applied via a high-density montage over the left parietal cortex at 1.5 mA for 20 min, while performance was assessed in an endogenous attention task. Task and tACS parameters were chosen to match those of previous studies reporting positive effects. Unlike these studies, we did not observe lateralized parietal alpha tACS to affect attention deployment or visual processing across the hemifields as compared to sham. Likewise, additional resting electroencephalography immediately offline to tACS did not reveal any notable effects on individual alpha power or frequency. Our study emphasizes the need for more replication studies and systematic investigations of the factors that drive tACS effects.

Top-down control of visual cortex by the frontal eye fields through oscillatory realignment.

Voluntary allocation of visual attention is controlled by top-down signals generated within the Frontal Eye Fields (FEFs) that can change the excitability of lower-level visual areas. However, the mechanism through which this control is achieved remains elusive. Here, we emulated the generation of an attentional signal using single-pulse transcranial magnetic stimulation to activate the FEFs and tracked its consequences over the visual cortex. First, we documented changes to brain oscillations using electroencephalography and found evidence for a phase reset over occipital sites at beta frequency. We then probed for perceptual consequences of this top-down triggered phase reset and assessed its anatomical specificity. We show that FEF activation leads to cyclic modulation of visual perception and extrastriate but not primary visual cortex excitability, again at beta frequency. We conclude that top-down signals originating in FEF causally shape visual cortex activity and perception through mechanisms of oscillatory realignment.

Decoupling of Early V5 Motion Processing from Visual Awareness: A Matter of Velocity as Revealed by Transcranial Magnetic Stimulation.

Motion information can reach V5/MT through two parallel routes: one conveying information at early latencies through a direct subcortical route and the other reaching V5 later via recurrent projections through V1. Here, we tested the hypothesis that input via the faster direct pathway depends on motion characteristics. To this end, we presented motion stimuli to healthy human observers at different velocities (4.4°/sec vs. 23°/sec) with static stimuli as controls while applying transcranial magnetic stimulation (TMS) pulses over V5 or V1. We probed for TMS interference with objective (two-alternative forced choice [2AFC]) and subjective (awareness) measures of motion processing at six TMS delays from stimulus onset (poststimulus window covered: ∼27-160 msec). Our results for V5-TMS showed earlier interference with objective performance for fast motion (53.3 msec) than slow motion (80 msec) stimuli. Importantly, TMS-induced decreases in objective measures of motion processing did correlate with decreases in subjective measures for slow but not fast motion stimuli. Moreover, V1-TMS induced a temporally unspecific interference with visual processing as it impaired the processing of both motion and static stimuli at the same delays. These results are in accordance with fast moving stimuli reaching V5 through a different route than slow moving stimuli. The differential latencies and coupling to awareness suggest distinct involvement of a direct (i.e., colliculo-extrastriate) connection bypassing V1 depending on stimulus velocity (fast vs. slow). Implication of a direct pathway in the early processing of fast motion may have evolved through its behavioral relevance.

Impaired peripheral reaching and on-line corrections in patient DF: Optic ataxia with visual form agnosia.

An influential model of vision suggests the presence of two visual streams within the brain: a dorsal occipito-parietal stream which mediates action and a ventral occipito-temporal stream which mediates perception. One of the cornerstones of this model is DF, a patient with visual form agnosia following bilateral ventral stream lesions. Despite her inability to identify and distinguish visual stimuli, DF can still use visual information to control her hand actions towards these stimuli. These observations have been widely interpreted as demonstrating a double dissociation from optic ataxia, a condition observed after bilateral dorsal stream damage in which patients are unable to act towards objects that they can recognize. In Experiment 1, we investigated how patient DF performed on the classical diagnostic task for optic ataxia, reaching in central and peripheral vision. We replicated recent findings that DF is remarkably inaccurate when reaching to peripheral targets, but not when reaching in free vision. In addition we present new evidence that her peripheral reaching errors follow the optic ataxia pattern increasing with target eccentricity and being biased towards fixation. In Experiments 2 and 3, for the first time we examined DF's on-line control of reaching using a double-step paradigm in fixation-controlled and free-vision versions of the task. DF was impaired when performing fast on-line corrections on all conditions tested, similarly to optic ataxia patients. Our findings question the long-standing assumption that DF's dorsal visual stream is functionally intact and that her on-line visuomotor control is spared. In contrast, in addition to visual form agnosia, DF also has visuomotor symptoms of optic ataxia which are most likely explained by bilateral damage to the superior parietal-occipital cortex (SPOC). We thus conclude that patient DF can no longer be considered as an appropriate single-case model for testing the neural basis of perception and action dissociations.

Parieto-occipital cortex shows early target selection to faces in a reflexive orienting task.

It is well established that human faces induce stronger involuntary orienting responses than other visual objects. Yet, the timing of this preferential orienting response at the neural level is still unknown. Here, we used an antisaccade paradigm to investigate the neural dynamics preceding the onset of reflexive and voluntary saccades elicited by human faces and nonface visual objects, normalized for their global low-level visual properties. High-density event-related potentials (ERPs) were recorded in observers as they performed interleaved pro- and antisaccades toward a lateralized target. For reflexive saccades, we report an ERP modulation specific to faces as early as 40-60 ms following stimulus onset over parieto-occipital sites, further predicting the speed of saccade execution. This was not linked to differences in the programming of the saccadic eye movements, as it occurred early in time. For the first time, we present electrophysiological evidence of early target selection to faces in reflexive orienting responses over parieto-occipital cortex that facilitates the triggering of saccades toward faces. We argue for a 2-stage process in the representation of a face in involuntary spatial orienting with an initial, rapid implicit processing of the visual properties of a face, followed by subsequent stimulus categorization depicted by the N170 component.

Early event-related cortical activity originating in the frontal eye fields and inferior parietal lobe predicts the occurrence of correct and error saccades.

Although the cortical circuitry underlying saccade execution has well been specified by neurophysiological and functional imaging studies, the temporal dynamics of cortical activity predicting the occurrence of voluntary or reflexive saccades in humans are largely unknown. Here, we examined electrophysiological activity preceding the onset of correct (i.e., voluntary) or error (i.e., reflexive) saccades in an oculomotor capture task. Participants executed saccades to lateralized visual targets while attempting to inhibit reflexive glances to abruptly appearing distracters. Since the visual display was identical for both types of saccades, different electrophysiological patterns preceding correct and error saccades could not be explained by low-level perceptual differences. Compared to correct saccades electrophysiological activity preceding error saccades showed significant differences of the scalp electric field and of voltage amplitudes at posterior electrodes. In addition, though error saccades had significantly shorter latency than correct saccades a prolonged topographic configuration of electric potentials prior to error saccades was found ∼120-140 ms following target onset. In agreement with the known asymmetry in hemispheric dominance for spatial attention, distinct electrophysiological patterns were only found for leftward saccades. While error saccades were associated with stronger activity in the right Frontal Eye Field, correct saccades were preceded by stronger activity in the inferior parietal lobule. These findings suggest that selection of the saccade target in a conflicting situation is determined by early top-down biases originating in frontal and parietal cortical regions critical for spatial attention and saccade programming.

ERP correlates of word production before and after stroke in an aphasic patient.

Changes in brain activity characterizing impaired speech production after brain damage have usually been investigated by comparing aphasic speakers with healthy subjects because prestroke data are normally not available. However, when interpreting the results of studies of stroke patients versus healthy controls, there is an inherent difficulty in disentangling the contribution of neuropathology from other sources of between-subject variability. In the present work, we had an unusual opportunity to study an aphasic patient with severe anomia who had incidentally performed a picture naming task in an ERP study as a control subject one year before suffering a left hemisphere stroke. The fortuitous recording of this patient's brain activity before his stroke allows direct comparison of his pre- and poststroke brain activity in the same language production task. The subject did not differ from other healthy subjects before his stroke, but presented major electrophysiological differences after stroke, both in comparison to himself before stroke and to the control group. ERP changes consistently appeared after stroke in a specific time window starting about 250 msec after picture onset, characterized by a single divergent but stable topographic configuration of the scalp electric field associated with a cortical generator abnormally limited to left temporal posterior perilesional areas. The patient's pattern of anomia revealed a severe lexical-phonological impairment and his ERP responses diverged from those of healthy controls in the time window that has previously been associated with lexical-phonological processes during picture naming. Given that his prestroke ERPs were indistinguishable from those of healthy controls, it seems highly likely that the change in his poststroke ERPs is due to changes in language production processes as a consequence of stroke. The patient's neurolinguistic deficits, combined with the ERPs results, provide unique evidence for the role of left temporal cortex in lexical-phonological processing from about 250 to 450 msec during word production.

Looking away from faces: influence of high-level visual processes on saccade programming.

Human faces capture attention more than other visual stimuli. Here we investigated whether such face-specific biases rely on automatic (involuntary) or voluntary orienting responses. To this end, we used an anti-saccade paradigm, which requires the ability to inhibit a reflexive automatic response and to generate a voluntary saccade in the opposite direction of the stimulus. To control for potential low-level confounds in the eye-movement data, we manipulated the high-level visual properties of the stimuli while normalizing their global low-level visual properties. Eye movements were recorded in 21 participants who performed either pro- or anti-saccades to a face, car, or noise pattern, randomly presented to the left or right of a fixation point. For each trial, a symbolic cue instructed the observer to generate either a pro-saccade or an anti-saccade. We report a significant increase in anti-saccade error rates for faces compared to cars and noise patterns, as well as faster pro-saccades to faces and cars in comparison to noise patterns. These results indicate that human faces induce stronger involuntary orienting responses than other visual objects, i.e., responses that are beyond the control of the observer. Importantly, this involuntary processing cannot be accounted for by global low-level visual factors.

Abnormal cortical network activation in human amnesia: A high-resolution evoked potential study.

Little is known about how human amnesia affects the activation of cortical networks during memory processing. In this study, we recorded high-density evoked potentials in 12 healthy control subjects and 11 amnesic patients with various types of brain damage affecting the medial temporal lobes, diencephalic structures, or both. Subjects performed a continuous recognition task composed of meaningful designs. Using whole-scalp spatiotemporal mapping techniques, we found that, during the first 200 ms following picture presentation, map configuration of amnesics and controls were indistinguishable. Beyond this period, processing significantly differed. Between 200 and 350 ms, amnesic patients expressed different topographical maps than controls in response to new and repeated pictures. From 350 to 550 ms, healthy subjects showed modulation of the same maps in response to new and repeated items. In amnesics, by contrast, presentation of repeated items induced different maps, indicating distinct cortical processing of new and old information. The study indicates that cortical mechanisms underlying memory formation and re-activation in amnesia fundamentally differ from normal memory processing.

Re-evaluating the time course of gender and phonological encoding during silent monitoring tasks estimated by ERP: serial or parallel processing?

Neurolinguistic and psycholinguistic studies suggest that grammatical (gender) and phonological information are retrieved independently and that gender can be accessed before phonological information. This study investigated the relative time courses of gender and phonological encoding using topographic evoked potentials mapping methods. Event-related brain potentials (ERPs) were recorded using a high resolution electroencephalogram (EEG) system (128 channels) during gender and phoneme monitoring in silent picture naming. Behavioural results showed similar reaction times (RT) between gender and word onset (first phoneme) monitoring, and longer RT when monitoring the second syllable onset. Temporal segmentation analysis (defining dominant map topographies using cluster analysis) revealed no timing difference between gender monitoring and word onset monitoring: both effects fall within the same time window at about 270-290 ms after picture presentation. Monitoring a second syllable onset generated a later effect at about 480 ms. Direct comparison between gender and first phoneme monitoring revealed a difference of only 10 ms between tasks at approximately 200 ms. Taken together, these results suggest that lemma retrieval and phonological encoding may proceed in parallel or overlap. Word onset is retrieved simultaneously with gender, while the longer RT and the later ERP effect for second syllable onset reflect that segmental encoding continues incrementally to the following phonemes.

Electrophysiological correlates of different anomic patterns in comparison with normal word production.

Different forms of anomia are observed in aphasia, which can be related to impaired semantic, lexical or phonological processes. In the present study, we analysed electrophysiological correlates of different patterns of anomia in six aphasic speakers. Event-related potentials (ERPs) were recorded during picture naming in each anomic speaker and in 15 healthy controls. Waveform analysis and temporal segmentation indicated a difference between high and low frequency words in the control group between 270 and 330 msec after picture onset. The ERPs recorded in the patients were compared to the control group. The time-windows of divergent ERP correlates were very similar between successful and erroneous naming, but they were differently distributed in the 6 patients. Two patients with conduction aphasia and impaired phonological encoding had normal electro-cortical activity during the first 300 msec and abnormal patterns between 300 and 450 msec. Two patients with lexical-semantic impairment had earlier ERP abnormalities starting immediately after visual processes. The two patients with less severe anomia and preponderance of omission errors displayed abnormal ERPs between 280 and 350 msec. These results indicate that abnormal electro-cortical correlates of anomic profiles can be observed in different time-windows, which seem to correspond to the time course of the impaired encoding processes.

Neural transition from short- to long-term memory and the medial temporal lobe: a human evoked-potential study.

Recent studies indicated that the human medial temporal lobe (MTL) may not only be important for long-term memory consolidation but also for certain forms of short-term memory. In this study, we explored the interplay between short- and long-term memory using high-density event-related potentials. We found that pictures immediately repeated after an unfilled interval were better recognized than pictures repeated after intervening items. After 30 min, however, the immediately repeated pictures were significantly less well recognized than pictures repeated after intervening items. This processing advantage at immediate repetition but disadvantage for long-term storage had an electrophysiological correlate: spatiotemporal analysis showed that immediate repetition induced a strikingly different electrocortical response after 200-300 ms, with inversed polarity, than new stimuli and delayed repetitions. Inverse solutions indicated that this difference reflected transient activity in the MTL. The findings demonstrate behavioral and electrophysiological dissociation between recognition during active maintenance and recognition after intervening items. Processing of novel information seems to immediately initiate a consolidation process, which remains vulnerable during active maintenance and increases its effectiveness during off-line processing.

Instinctive modulation of cognitive behavior: a human evoked potential study.

Successful adaptive behavior requires fast information processing. Behavioral switches may be necessary in response to threatening stimuli or when anticipated outcomes fail to occur. In this study, we explored the cortical processing of these two components using high-resolution evoked potentials. Subjects made a reversal learning task where they had to predict which one of two faces had a target stimulus on the nose. We found early electrocortical differences at 100-200 ms depending on whether the target stimulus was a spider or a disk. Source estimation indicated that this distinction was mediated by an anterior medial temporal region including the amygdala and adjacent cortex. When a switch to the alternate face was required, there was a discrete early electrocortical correlate after 200 ms, mediated by ventromedial prefrontal areas. Continued validity of stimulus-target associations was signaled at 400-520 ms, mediated by the parahippocampal region. The study indicates rapid serial processing of innate emotional quality, then cognitive-behavioral relevance of stimuli, mediated by limbic and paralimbic structures.

Time course of evoked-potential changes in different forms of anomia in aphasia.

Impaired word production after brain damage can be due to impairment at lexical-semantic or at lexical-phonological levels of word encoding. These processes are thought to involve different brain regions and to have different time courses. The present study investigated the time course of electrophysiological correlates of anomia in 16 aphasic speakers, divided in two subgroups according to their anomic pattern (8 with lexical-semantic impairment and 8 with lexical-phonological impairment), in comparison to 16 healthy control subjects performing the same picture naming task. Differences in amplitudes and in topographic maps between groups were differently distributed when the whole heterogeneous group of aphasic patients was compared to the control group and when the two more homogeneous subgroups of anomic patients were analyzed. The entire aphasic group expressed different waveforms and topographic patterns than the control group starting about 100 msec after picture presentation. When two subgroups of aphasic patients are considered according to the underlying cognitive impairment, early event-related potential (ERP) abnormalities (100-250 msec) appeared only in the lexical-semantic subgroup, whereas later ERP abnormalities (300-450 msec) occurred only in the lexical-phonological subgroup. These results indicate that the time windows of ERP abnormalities vary depending on the underlying anomic impairment. Moreover, the findings give support to current hypotheses on the time course of processes involved in word production during picture naming.

Normalisation and increase of abnormal ERP patterns accompany recovery from aphasia in the post-acute stage.

Electrophysiological correlates of recovery from anomia were analysed in four aphasic patients in the post-acute stage. Event-related potentials (ERPs) were recorded during picture naming at baseline and after a period of therapy for anomia. All patients had severe anomia at baseline assessment and improved significantly in naming during the study period. Waveform analyses and temporal segmentation were carried out on the ERPs of each patient in comparison with 15 healthy control subjects. Normalisation as well as an increase of abnormal electrophysiological correlates accompanied recovery. An increase of abnormal amplitudes appeared in a patient with semantic impairment during the first 300 ms after picture onset, while only normalisation of amplitudes and topographic maps accompanied recovery in the three patients with lexical-phonological impairment in this early time-window. Abnormal amplitudes and topographic maps emerged during recovery in the patients with lexical-phonological impairment in later time-windows, starting between 250 and 300 ms. Follow-up ERP recordings carried out 6 months later in two of them showed normalisation of amplitudes and persistence of abnormal maps. The results suggest that electrophysiological changes accompanying recovery from anomia in the post-acute stage are observed in specific time-windows, probably corresponding to different encoding processes and that recovery correlates with normalisation of EEG patterns as well as with the emergence of abnormalities, which presumably indicates compensation mechanisms of specific encoding processes.

Early cortical response to behaviorally relevant absence of anticipated outcomes: a human event-related potential study.

Animals with lesions of the orbitofrontal cortex (OFC) have an extinction and reversal learning deficit. Humans with OFC lesions have similar deficits and often continue to act according to currently inappropriate memories. We tested when the human brain distinguishes between confirmed and negated outcomes of anticipations. Eleven participants predicted behind which one of two rectangles an object drawing was hidden while their cerebral activity was recorded from 123 surface electrodes. We found that absence of the predicted outcome induced specific electrical field topographies between 190 ms-300 ms and 380 ms-600 ms. Behaviorally irrelevant deviation from predicted outcomes did not induce these alterations. Distributed linear inverse solutions indicated that the source of the early electric field topography after negated predictions differed by additional left ventrolateral prefrontal activation. The late differences in electrical field topographies were characterized by the selective absence of a processing stage in response to negated predictions. The study indicates early, specific cortical processing of behaviorally relevant absence of predicted outcomes.

Electrophysiological correlates of deficient encoding in a case of post-anoxic amnesia.

Little is known about the initial stages of information processing in amnesia as compared to normal memory. In this study, we used electrical spatiotemporal mapping to compare cortical activation during encoding and recognition in a 56-year-old patient with severe, chronic post-anoxic amnesia and an age-matched control group. Event-related potentials were recorded as the subjects performed a continuous recognition task composed of meaningful designs. Activation in the control group rapidly progressed through eight different electrocortical configurations over 700 ms after onset of new stimuli. In contrast, activation in the amnesic patient was highly monotonous: it showed varying electrocortical patterns only during the first 150 ms but then remained abnormally stable for the remainder of the analysed time window. Electrical source localisation revealed that the patient failed to activate distributed cortical networks and that his processing was confined to visual areas. The present study suggests that the rapid activation of distributed cortical networks is critical for efficient encoding.

Early cortical distinction between memories that pertain to ongoing reality and memories that don't.

Patients with anterior limbic lesions, in particular of the posterior orbitofrontal cortex, often act on the basis of memories that do not relate to ongoing reality and justify their behavior with invented stories that can mostly be traced back to real events (spontaneous confabulation). Recent studies demonstrated that the patients fail to suppress activated memory traces that do not pertain to ongoing reality. In the present study, we used a similar paradigm and high-resolution event-related potentials to explore when this suppression happens. Healthy subjects made two runs of a continuous recognition task, composed of the same set of pictures, and were requested to indicate picture recurrences only within the ongoing run. Thus, performance in the first run depends on new learning, whereas the second run requires the ability to realize whether a picture is solely familiar from its occurrence in the previous run ('distracter') or whether it has already appeared in the ongoing second run ('target'). We find that correct rejection (suppression) of currently irrelevant pictures (distracters of run 2) is associated with absent negative deflection of a frontal potential and absence of a specific cortical potential map configuration after 220-300 ms. By contrast, learning and recognition of repeatedly presented information is associated with cortical amplitude modulation after 400-480 ms. These findings indicate that by the time the content of a mental association is recognized and consolidated, its cortical representation has already been adjusted according to whether it relates to ongoing reality or not. This sequence may also explain the ability to distinguish between the memory of a true event and the memory of a thought.