Association between retinal and cortical visual electrophysiological impairments in schizophrenia.

BACKGROUND: Electrophysiological impairments in the magnocellular visual system have been reported among patients with schizophrenia, but previous theories proposed that these deficits may begin in the retina. We therefore sought to evaluate the potential contribution of the retina by comparing retinal and cortical visual electrophysiological impairments between patients with schizophrenia and healthy controls. METHODS: We recruited patients with schizophrenia and age- and sex-matched healthy controls. We recorded the P100 amplitude and latency using electroencephalography (EEG) while projecting low (0.5 cycles/degree) or high (15 cycles/degree) spatial frequency gratings at a temporal frequency of 0 Hz or 8 Hz. We compared the P100 results with previous results for retinal ganglion cell activity (N95) in these participants. We analyzed data using repeated-measures analysis of variance and correlation analyses. RESULTS: We recruited 21 patients with schizophrenia and 29 age- and sex-matched healthy controls. Results showed decreased P100 amplitude and increased P100 latency among patients with schizophrenia compared with healthy controls (p < 0.05). Analyses reported the main effects of spatial and temporal frequency but no interaction effects of spatial or temporal frequency by group. Moreover, correlation analysis indicated a positive association between P100 latency and previous retinal results for N95 latency in the schizophrenia group (p < 0.05). DISCUSSION: Alterations in the P100 wave among patients with schizophrenia are consistent with the deficits in early visual cortical processing shown in the literature. These deficits do not seem to correspond to an isolated magnocellular deficit but appear to be associated with previous retinal measurements. Such an association emphasizes the role of the retina in the occurrence of visual cortical abnormalities in schizophrenia. Studies with coupled electroretinography-EEG measurements are now required to further explore these findings. CLINICAL TRIALS REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02864680.

Naming impairments evoked by focal cortical electrical stimulation in the ventral temporal cortex correlate with increased functional connectivity.

BACKGROUND: High-frequency cortical electrical stimulations (HF-CES) are the gold standard for presurgical functional mapping. In the dominant ventral temporal cortex (VTC) HF-CES can elicit transient naming impairment (eloquent sites), defining a basal temporal language area (BTLA). OBJECTIVE: Whether naming impairments induced by HF-CES within the VTC are related to a specific pattern of connectivity of the BTLA within the temporal lobe remains unknown. We addressed this issue by comparing the connectivity of eloquent and non-eloquent sites from the VTC using cortico-cortical evoked potentials (CCEP). METHODS: Low frequency cortical electrical stimulations (LF-CES) were used to evoke CCEP in nine individual brains explored with Stereo-Electroencephalography. We compared the connectivity of eloquent versus non eloquent sites within the VTC using Pearson's correlation matrix. RESULTS: Overall, within the VTC, eloquent sites were associated with increased functional connectivity compared to non-eloquent sites. Among the VTC structures, this pattern holds true for the inferior temporal gyrus and the parahippocampal gyrus while the fusiform gyrus specifically showed a high connectivity in both non eloquent and eloquent sites. CONCLUSIONS: Our findings suggest that the cognitive effects of focal HF-CES are related to the functional connectivity properties of the stimulated sites, and therefore to the disturbance of a wide cortical network. They further suggest that functional specialization of a cortical region emerges from its specific pattern of functional connectivity. Cortical electrical stimulation functional mapping protocols including LF coupled to HF-CES could provide valuable data characterizing both local and distant functional architecture.

Impaired P100 among regular cannabis users in response to magnocellular biased visual stimuli.

Regular cannabis using causes vision impairment by affecting human retinal neurotransmission. However, studies less considered its impact on the subsequent visual cortical processing, key feature for the integration of the visual signal in brain. We aimed at investigating this purpose in regular cannabis users using spatial frequencies and temporal frequencies filtered visual stimuli. We recruited 45 regular cannabis users and 25 age-matched controls. We recorded visual evoked potentials during the projection of low spatial frequency (0.5 cycles/degree) or high spatial frequency gratings (15 cycles/degree), which were presented statically (0 Hz) or dynamically (8 Hz). We analyzed the amplitude, latency, and area under the curve of both P100 and N170, best EEG markers for early visual processing. Data were compared between groups by repeated measures ANCOVA. Results showed a significant decrease in P100 amplitude among regular cannabis users in low spatial frequency (F(1,67) = 4.43; p = 0.04) and in dynamic condition (F(1,67) = 4.35; p = 0.04). Analysis also reported a decrease in P100 area under the curve in regular cannabis users to low spatial frequency (F(1,67) = 4.31; p = 0.04) and in dynamic condition (F(1,67) = 7.65; p < 0.01). No effect was found on P100 latency, N170 amplitude, latency, or area under the curve. We found alteration of P100 responses to low spatial frequency and dynamic stimuli in regular cannabis users. This result could be interpreted as a preferential magnocellular impairment where such deficit could be linked to glutamatergic dysfunction. As mentioned in the literature, visual and electrophysiological anomalies in schizophrenia are related to a magnocellular dysfunction. Further studies are needed to clarify electrophysiological deficits in both populations. CLINICAL TRIALS REGISTRATION: Electrophysiological Study of the Functioning of Magnocellular Visual Pathway in Regular Cannabis Users (CAUSA MAP). [NCT02864680; ID 2013-A00097-38]. https://clinicaltrials.gov/ct2/show/NCT02864680?cond=Cannabis&cntry=FR&draw=2&rank=1.

Conjoint fluctuations of PFC-mediated processes and behavior: An investigation of error-related neural mechanisms in relation to sustained attention.

The ability to detect errors, which derives from the medial prefrontal cortex (mPFC), is crucial to maintain attention over a long period of time. While impairment of this ability has been reported in patients with sustained attention disruption, the role mPFC-mediated processes play in the intra-individual fluctuation of sustained attention remains an open question. In this context, we computed the variance time course of reaction time (RT) of 42 healthy individuals to distinguish intra-individual periods of low and high performance instability, assumed to represent optimal and suboptimal attentional states, when performing a sustained Go/NoGo task. Analysis of the neurophysiological mechanisms of response monitoring revealed a specific reduction in the error-related negativity (ERN) amplitude and frontal midline theta power during periods of high compared to low RT variability, but only in individuals with a higher standard deviation of reaction time (SD-RT). Concerning post-error adaptation, an increase in the correct-related negativity (CRN) amplitude as well as the frontal lateral theta power on trials following errors was observed in individuals with lower SD-RT but not in those with higher SD-RT. Our results thus show that individuals with poor sustained attention ability exhibit altered post-error adaptation and attentional state-dependent efficiency of error monitoring. Conversely, individuals with good sustained attention performances retained their post-error adaptation and response monitoring regardless of the attentional periods. These findings reveal the critical role of the action-monitoring system in intra-individual behavioral stability and highlight the importance of considering attentional states when studying mPFC-mediated processes, especially in subjects with low sustained attention ability.

Investigation of electrophysiological precursors of attentional errors in schizophrenia: Toward a better understanding of abnormal proactive control engagement.

Impaired cognitive control has been associated with the occurrence of attentional errors in those with schizophrenia. However, the extent of altered proactive or reactive control underlying such errors is still unknown. Twenty-two patients with schizophrenia and 21 healthy matched controls performed a detection task (i.e., the continuous temporal expectancy task). Electrophysiological measures of proactive and reactive control were based on two periods of interest: during the target presentation (the critical window) and four trials before the critical window. Regarding the proactive mode, patients with schizophrenia exhibited a specific decrease in frontal midline theta power during the critical window before a miss compared to a correct detection. In contrast, the contingent negative variation amplitude was altered regardless of the response type, four trials before the critical window. Regarding the reactive mode, a reduced P3 amplitude was revealed later before a miss than a correct detection with differences apparent only two trials before the critical window in patients with schizophrenia, whereas it was observable up to four trials prior in healthy controls. Moreover, only the P3 amplitude reduction in patients with schizophrenia predicted the miss rate and was anti-correlated with the clinical symptoms. Thus, our results revealed a specific impairment of the proactive goal-updating process before an error and an altered implementation of the endogenous proactive mode engagement regardless of the response type. The results also highlighted the strong relationship between the disrupted reactive mode and the increased rate of attentional errors and severity of the clinical symptoms of schizophrenia.

Impaired Frontal Midline Theta During Periods of High Reaction Time Variability in Schizophrenia.

BACKGROUND: Impairment in cognitive control is one of the most significant cognitive deficits in schizophrenia. Although it has generally been associated with altered engagement of lateral and medial prefrontal cortices, how attention fluctuations affect this engagement is still not known. In this context, we explored sustained (or proactive) and transient (or reactive) control engagement by investigating frontal theta-band oscillations during periods of low- and high-performance instability, assumed to represent intraindividual attentional fluctuations. METHODS: A total of 25 patients with schizophrenia (16 males) and 25 healthy matched control subjects (18 males) performed a long-sustained Go/NoGo task coupled with electroencephalographic recording. Proactive control was explored through frontal lateral theta during trial-by-trial conflict (Go N-1/Go N+1), whereas reactive control was explored through frontal midline theta and the N2 component during current-trial conflict (Go/NoGo). Variance in the time course of reaction time (RT) was computed to identify periods of low and high RT variability in each subject. RESULTS: Patients with schizophrenia exhibited no frontal lateral theta activity regardless of the RT variability periods, whereas in control subjects, this activity was preserved only during periods of low RT variability (less error prone). During these periods, patients exhibited preserved midline frontal theta activity and N2. However, during high RT variability periods (more error prone), the midline theta activity was impaired in patients but preserved in control subjects. CONCLUSIONS: Our results reveal that the efficient engagement of reactive control in patients with schizophrenia and of proactive control in control subjects was state dependent. The findings highlight the importance of accounting for attentional fluctuations when investigating cognitive control impairment in schizophrenia.

Role of the supplementary motor area during reproduction of supra-second time intervals: An intracerebral EEG study.

The supplementary motor area (SMA) has been shown to be involved in interval timing but its precise role remains a matter of debate. The present study was aimed at examining, by means of intracerebral EEG recordings, the time course of the activity in this structure, as well as in other functionally connected cortical (frontal, cingulate, insular and temporal) areas, during a visual time reproduction task. Four patients undergoing stereo-electroencephalography (SEEG) for presurgical investigation of refractory focal epilepsy were enrolled. They were selected on the presence of depth electrodes implanted within the SMA. They were instructed to encode, keep in memory and then reproduce the duration (3, 5 and 7 s) of emotionally-neutral or negative pictures. Emotional stimuli were used with the aim of examining neural correlates of temporal distortions induced by emotion. Event-related potentials (ERPs) were analyzed during three periods: During and at the extinction of the target interval (TI) and at the beginning of the reproduction interval (RI). Electrophysiological data revealed an ERP time-locked to TI-offset whose amplitude varied monotonically with TI-duration. This effect was observed in three out of the four patients, especially within the SMA and the insula. It also involved the middle and anterior cingulate cortex, the superior, middle and inferior frontal gyri and the paracentral lobule. These effects were modulated by the prior TI-duration and predicted variations in temporal reproduction accuracy. In contrast, modulations of ERPs with TI-duration, emotion or temporal performance during the target or the reproduction interval were modest and less consistent across patients. These results demonstrate that, during reproduction of supra-second time intervals, the SMA, in concert with a fronto-insular network, is involved at the end of the target interval, and suggest a role in the duration categorization and decision making operations or alternatively in the preparedness of the timing of the future movement that will be executed during the reproduction phase.

Association between increased retinal background noise and co-occurrent regular cannabis and alcohol use.

BACKGROUND: Cannabis consumption is widespread across the world, and the co-occurrence of cannabis use and alcohol consumption is common. The study of background noise - resting-state neural activity, in the absence of stimulation - is an approach that could enable the neurotoxicity of these substances to be explored. Preliminary results have shown that delta-9-tetrahydrocannabinol (Δ9-THC) causes an increase in neural noise in the brain. Neurons in the brain and the retina share a neurotransmission system and have similar anatomical and functional properties. Retinal function, evaluated using an electroretinogram (ERG), may therefore reflect central neurochemistry. This study analyses retinal background noise in a population of regular co-occurrent cannabis and alcohol consumers. METHODS: We recorded the flash ERGs of 26 healthy controls and 45 regular cannabis consumers, separated into two groups based on their alcohol consumption: less than or equal to 4 glasses per week (CU ≤ 4) or strictly >4 glasses per week (CU >4). In order to extract the background noise, the Fourier transform of the pseudo-periodic and sinusoidal signals of the 3.0 flicker-response sequence was calculated. This sequence represents the vertical transmission of the signal from cones to bipolar cells. The magnitude of the background noise is defined as the average of the magnitudes of the two neighbouring harmonics: harmonic -1 (low frequency noise) and harmonic +1 (high frequency noise). RESULTS: The magnitude of harmonic -1 was significantly increased between the groups CU > 4 (6.78 (±1.24)) and CU ≤ 4 (5.69 (±1.80)) among regular users of cannabis and alcohol. A significant increase in the average magnitude of the two harmonics was found between the groups CU > 4 (5.12 (±0.92)) and CU ≤ 4 (4.36 (±1.14)). No significant difference was observed with regard to the magnitude of the harmonic +1. CONCLUSIONS: The increase in background noise may reflect the neurotoxicity of cannabis, potentiated by alcohol consumption, on retinal neurons dynamic. This neural disruption of the response generated by retinal stimulation may be attributable to altered neurotransmitter release.

Association between increased EEG signal complexity and cannabis dependence.

Both acute and regular cannabis use affects the functioning of the brain. While several studies have demonstrated that regular cannabis use can impair the capacity to synchronize neural assemblies during specific tasks, less is known about spontaneous brain activity. This can be explored by measuring EEG complexity, which reflects the spontaneous variability of human brain activity. A recent study has shown that acute cannabis use can affect that complexity. Since the characteristics of cannabis use can affect the impact on brain functioning, this study sets out to measure EEG complexity in regular cannabis users with or without dependence, in comparison with healthy controls. We recruited 26 healthy controls, 25 cannabis users without cannabis dependence and 14 cannabis users with cannabis dependence, based on DSM IV TR criteria. The EEG signal was extracted from at least 250 epochs of the 500ms pre-stimulation phase during a visual evoked potential paradigm. Brain complexity was estimated using Lempel-Ziv Complexity (LZC), which was compared across groups by non-parametric Kruskall-Wallis ANOVA. The analysis revealed a significant difference between the groups, with higher LZC in participants with cannabis dependence than in non-dependent cannabis users. There was no specific localization of this effect across electrodes. We showed that cannabis dependence is associated to an increased spontaneous brain complexity in regular users. This result is in line with previous results in acute cannabis users. It may reflect increased randomness of neural activity in cannabis dependence. Future studies should explore whether this effect is permanent or diminishes with cannabis cessation.

Discrimination of a medial functional module within the temporal lobe using an effective connectivity model: A CCEP study.

The temporal lobe is classically divided in two functional systems: the ventral visual pathway and the medial temporal memory system. However, their functional separation has been challenged by studies suggesting that the medial temporal lobe could be best understood as an extension of the hierarchically organized ventral visual pathway. Our purpose was to investigate (i) whether cerebral regions within the temporal lobe could be grouped into distinct functional assemblies, and (ii) which regions were central within these functional assemblies. We studied low intensity and low frequency electrical stimulations (0.5 mA, 1 Hz, 4 ms) performed during sixteen pre-surgical intracerebral EEG investigations in patients with medically intractable temporal or temporo-occipital lobe epilepsies. Eleven regions of interest were delineated per anatomical landmarks such as gyri and sulci. Effective connectivity based on electrophysiological feature (amplitude) of cortico-cortical evoked potentials (CCEPs) was evaluated and subjected to graph metrics. The amplitudes discriminated one medial module where the hippocampus could act as a signal amplifier. Mean amplitudes of CCEPs in regions of the temporal lobe showed a generalized Pareto distribution of probability suggesting neural synchronies to be self-organized critically. Our description of effective interactions within the temporal lobe provides a regional electrophysiological model of effective connectivity which is discussed in the context of the current hypothesis of pattern completion.

How functional coupling between the auditory cortex and the amygdala induces musical emotion: a single case study.

Music is a sound structure of remarkable acoustical and temporal complexity. Although it cannot denote specific meaning, it is one of the most potent and universal stimuli for inducing mood. How the auditory and limbic systems interact, and whether this interaction is lateralized when feeling emotions related to music, remains unclear. We studied the functional correlation between the auditory cortex (AC) and amygdala (AMY) through intracerebral recordings from both hemispheres in a single patient while she listened attentively to musical excerpts, which we compared to passive listening of a sequence of pure tones. While the left primary and secondary auditory cortices (PAC and SAC) showed larger increases in gamma-band responses than the right side, only the right side showed emotion-modulated gamma oscillatory activity. An intra- and inter-hemisphere correlation was observed between the auditory areas and AMY during the delivery of a sequence of pure tones. In contrast, a strikingly right-lateralized functional network between the AC and the AMY was observed to be related to the musical excerpts the patient experienced as happy, sad and peaceful. Interestingly, excerpts experienced as angry, which the patient disliked, were associated with widespread de-correlation between all the structures. These results suggest that the right auditory-limbic interactions result from the formation of oscillatory networks that bind the activities of the network nodes into coherence patterns, resulting in the emergence of a feeling.

Intracerebral electrical stimulation of a face-selective area in the right inferior occipital cortex impairs individual face discrimination.

During intracerebral stimulation of the right inferior occipital cortex, a patient with refractory epilepsy was transiently impaired at discriminating two simultaneously presented photographs of unfamiliar faces. The critical electrode contact was located in the most posterior face-selective brain area of the human brain (right "occipital face area", rOFA) as shown both by low- (ERP) and high-frequency (gamma) electrophysiological responses as well as a face localizer in fMRI. At this electrode contact, periodic visual presentation of 6 different faces by second evoked a larger electrophysiological periodic response at 6 Hz than when the same face identity was repeated at the same rate. This intracerebral EEG repetition suppression effect was markedly reduced when face stimuli were presented upside-down, a manipulation that impairs individual face discrimination. These findings provide original evidence for a causal relationship between the face-selective right inferior occipital cortex and individual face discrimination, independently of long-term memory representations. More generally, they support the functional value of electrophysiological repetition suppression effects, indicating that these effects can be used as an index of a necessary neural representation of the changing stimulus property.

A comparison of methods for assessing alpha phase resetting in electrophysiology, with application to intracerebral EEG in visual areas.

There are two competing views on the mechanisms underlying the generation of visual evoked potentials/fields in EEG/MEG. The classical hypothesis assumes an additive wave on top of background noise. Another hypothesis states that the evoked activity can totally or partially arise from a phase resetting of the ongoing alpha rhythm. There is no consensus however, on the best tools for distinguishing between these two hypotheses. In this study, we have tested different measures on a large series of simulations under a variety of scenarios, involving in particular trial-to-trial variability and different dynamics of ongoing alpha rhythm. No single measure or set of measures was found to be necessary or sufficient for defining phase resetting in the context of our simulations. Still, simulations permitted to define criteria that were the most reliable in practice for distinguishing additive and phase resetting hypotheses. We have then applied these criteria on intracerebral EEG data recordings in the visual areas during a visual discrimination task. We investigated the intracerebral channels that presented both ERP and ongoing alpha oscillations (n=37). Within these channels, a total of 30% fulfilled phase resetting criteria during the generation of the visual evoked potential, based on criteria derived from simulations. Moreover, 19% of the 37 channels presented dependence of the ERP on the level of pre-stimulus alpha. Only 5% of channels fulfilled both the simulation-related criteria and dependence on baseline alpha level. Our simulation study points out to the difficulty of clearly assessing phase resetting based on observed macroscopic electrophysiological signals. Still, some channels presented an indication of phase resetting in the context of our simulations. This needs to be confirmed by further work, in particular at a smaller recording scale.