Yvonne Höller

Visual P2 component is related to theta phase-locking

In this study we investigated the hypothesis whether P2-related differences tested in a visual priming paradigm are associated with theta phase-locking. We recorded the EEG from 31 electrodes and calculated phase-locking index and total power differences for frequencies between 2 and 20 Hz. ERPs (event-related potentials) were analyzed for P1, N1 and P2 components. P2 showed strongest task-related amplitude differences between congruent and incongruent targets. A source analyses was performed for the P2 component using sLoreta that revealed local generators of the P2 in parieto-occipital regions. Phase-locking analyses showed specific effects in the theta range (4-6 Hz) appearing in time windows at around the P2 component. We draw the conclusion that phase-locked theta reflect top-down regulation processes mediating information between memory systems and is in part involved in the modulation of the P2 component.

Functional brain reorganization after spinal cord injury: Systematic review of animal and human studies

Plastic changes of neural circuits occur after spinal cord injury (SCI) at various level of the central nervous system. In this review we will focus on delineating the pathophysiological mechanisms of the brain plasticity changes following SCI, based on the existing neuroimaging and neurophysiological evidence in experimental models and humans. In animal experiments, reorganization of the sensory topography as well as of the topographical map of primary motor and premotor cortices have been reported in several studies. Brain imaging revealed that cortical representation in response to spared forelimb stimulation early enlarges and invades adjacent sensory-deprived hind limb territory. Electrophysiological studies demonstrated that the deafferentation due to SCI can immediately change the state of large cortical networks within 1h, and that these changes play a critical role in the functional reorganization after SCI. In humans neuroimaging also showed shifts of functional motor and sensory cortical representations that relate to the severity of SCI. In patients with cervical SCI, cortical forearm motor representations, as assessed by means of transcranial magnetic stimulation, may reorganize towards the intrinsic hand motor representation to maximize output to muscles of the impaired forearm. Excessive or aberrant reorganisation of cerebral cortex may also have pathological consequences, such as phantom sensations or neuropathic pain. Integrated neuroimaging and neurophysiological approaches may also lead to the development of new therapeutic strategies, which have the potential of enhancing sensorimotor recovery in patients with SCI.

Deactivation of the Default Mode Network as a Marker of Impaired Consciousness: An fMRI Study

Diagnosis of patients with a disorder of consciousness is very challenging. Previous studies investigating resting state networks demonstrate that 2 main features of the so-called default mode network (DMN), metabolism and functional connectivity, are impaired in patients with a disorder of consciousness. However, task-induced deactivation – a third main feature of the DMN – has not been explored in a group of patients. Deactivation of the DMN is supposed to reflect interruptions of introspective processes. Seventeen patients with unresponsive wakefulness syndrome (UWS, former vegetative state), 8 patients in minimally conscious state (MCS), and 25 healthy controls were investigated with functional magnetic resonance imaging during a passive sentence listening task. Results show that deactivation in medial regions is reduced in MCS and absent in UWS patients compared to healthy controls. Moreover, behavioral scores assessing the level of consciousness correlate with deactivation in patients. On single-subject level, all control subjects but only 2 patients in MCS and 6 with UWS exposed deactivation. Interestingly, all patients who deactivated during speech processing (except for one) showed activation in left frontal regions which are associated with conscious processing. Our results indicate that deactivation of the DMN can be associated with the level of consciousness by selecting those who are able to interrupt ongoing introspective processes. In consequence, deactivation of the DMN may function as a marker of consciousness.

Functional similarities between the P1 component and alpha oscillations

The present study attempts to demonstrate functional similarities between the P1 component of event‐related potentials and alpha oscillations that are predicted by the ‘alpha inhibition‐timing’ hypothesis. On the basis of findings showing that the frequency characteristic of the P1 component lies in the alpha range and that alpha oscillation is functionally associated with inhibition, we predict that the P1 component also reflects inhibitory processes. This hypothesis is tested in two experiments, a spatial‐cuing task and a visual‐semantic categorization task. The results of the cuing task demonstrate that in a similar way as alpha power, the P1 component is larger over task‐irrelevant ipsilateral sites. For the categorization task, we found that the P1 component, in a similar way to alpha oscillations, is larger for task‐irrelevant, distorted pictures. We conclude that the P1 component may be generated at least in part by evoked alpha oscillations and reflects inhibition in the sense of suppressing task‐irrelevant processes.

Altered network properties of the fronto-parietal network and the thalamus in impaired consciousness☆

Recovery of consciousness has been associated with connectivity in the frontal cortex and parietal regions modulated by the thalamus. To examine this model and to relate alterations to deficits in cognitive functioning and conscious processing, we investigated topological network properties in patients with chronic disorders of consciousness recovered from coma. Resting state fMRI data of 34 patients with unresponsive wakefulness syndrome and 25 in minimally conscious state were compared to 28 healthy controls. We investigated global and local network characteristics. Additionally, behavioral measures were correlated with the local metrics of 28 regions within the fronto-parietal network and the thalamus. In chronic disorders of consciousness, modularity at the global level was reduced suggesting a disturbance in the optimal balance between segregation and integration. Moreover, network properties were altered in several regions which are associated with conscious processing (particularly, in medial parietal, and frontal regions, as well as in the thalamus). Between minimally conscious and unconscious patients the local efficiency of medial parietal regions differed. Alterations in the thalamus were particularly evident in non-conscious patients. Most of the regions affected in patients with impaired consciousness belong to the so-called ‘rich club’ of highly interconnected central nodes. Disturbances in their topological characteristics have severe impact on information integration and are reflected in deficits in cognitive functioning probably leading to a total breakdown of consciousness.

High-frequency oscillations in epilepsy and surgical outcome. A meta-analysis

High frequency oscillations (HFOs) are estimated as a potential marker for epileptogenicity. Current research strives for valid evidence that these HFOs could aid the delineation of the to-be resected area in patients with refractory epilepsy and improve surgical outcomes. In the present meta-analysis, we evaluated the relation between resection of regions from which HFOs can be detected and outcome after epilepsy surgery. We conducted a systematic review of all studies that related the resection of HFO-generating areas to postsurgical outcome. We related the outcome (seizure freedom) to resection ratio, that is, the ratio between the number of channels on which HFOs were detected and, among these, the number of channels that were inside the resected area. We compared the resection ratio between seizure free and not seizure free patients. In total, 11 studies were included. In 10 studies, ripples (80–200 Hz) were analyzed, and in 7 studies, fast ripples (>200 Hz) were studied. We found comparable differences (dif) and largely overlapping confidence intervals (CI) in resection ratios between outcome groups for ripples (dif = 0.18; CI: 0.10–0.27) and fast ripples (dif = 0.17; CI: 0.01–0.33). Subgroup analysis showed that automated detection (dif = 0.22; CI: 0.03–0.41) was comparable to visual detection (dif = 0.17; CI: 0.08–0.27). Considering frequency of HFOs (dif = 0.24; CI: 0.09–0.38) was related more strongly to outcome than considering each electrode that was showing HFOs (dif = 0.15; CI = 0.03–0.27). The effect sizes found in the meta-analysis are small but significant. Automated detection and application of a detection threshold in order to detect channels with a frequent occurrence of HFOs is important to yield a marker that could be useful in presurgical evaluation. In order to compare studies with different methodological approaches, detailed and standardized reporting is warranted.

Impaired consciousness is linked to changes in effective connectivity of the posterior cingulate cortex within the default mode network

The intrinsic connectivity of the default mode network has been associated with the level of consciousness in patients with severe brain injury. Especially medial parietal regions are considered to be highly involved in impaired consciousness. To better understand what aspect of this intrinsic architecture is linked to consciousness, we applied spectral dynamic causal modeling to assess effective connectivity within the default mode network in patients with disorders of consciousness. We included 12 controls, 12 patients in minimally conscious state and 13 in vegetative state in this study. For each subject, we first defined the four key regions of the default mode network employing a subject-specific independent component analysis approach. The resulting regions were then included as nodes in a spectral dynamic causal modeling analysis in order to assess how the causal interactions across these regions as well as the characteristics of neuronal fluctuations change with the level of consciousness. The resulting pattern of interaction in controls identified the posterior cingulate cortex as the main driven hub with positive afferent but negative efferent connections. In patients, this pattern appears to be disrupted. Moreover, the vegetative state patients exhibit significantly reduced self-inhibition and increased oscillations in the posterior cingulate cortex compared to minimally conscious state and controls. Finally, the degree of self-inhibition and strength of oscillation in this region is correlated with the level of consciousness. These findings indicate that the equilibrium between excitatory connectivity towards posterior cingulate cortex and its feedback projections is a key aspect of the relationship between alterations in consciousness after severe brain injury and the intrinsic functional architecture of the default mode network. This impairment might be principally due to the disruption of the mechanisms underlying self-inhibition and neuronal oscillations in the posterior cingulate cortex.

Thiamine Deficiency Induced Neurochemical, Neuroanatomical, and Neuropsychological Alterations: A Reappraisal

Nutritional deficiency can cause, mainly in chronic alcoholic subjects, the Wernicke encephalopathy and its chronic neurological sequela, the Wernicke-Korsakoff syndrome (WKS). Long-term chronic ethanol abuse results in hippocampal and cortical cell loss. Thiamine deficiency also alters principally hippocampal- and frontal cortical-dependent neurochemistry; moreover in WKS patients, important pathological damage to the diencephalon can occur. In fact, the amnesic syndrome typical for WKS is mainly due to the damage in the diencephalic-hippocampal circuitry, including thalamic nuclei and mammillary bodies. The loss of cholinergic cells in the basal forebrain region results in decreased cholinergic input to the hippocampus and the cortex and reduced choline acetyltransferase and acetylcholinesterase activities and function, as well as in acetylcholine receptor downregulation within these brain regions. In this narrative review, we will focus on the neurochemical, neuroanatomical, and neuropsychological studies shedding light on the effects of thiamine deficiency in experimental models and in humans.

Preserved oscillatory response but lack of mismatch negativity in patients with disorders of consciousness

OBJECTIVE The diagnostic validity of non-phase-locked oscillations (NPLOs) and mismatch negativity (MMN) in an oddball task for assessing attentional reactivity in patients with disordered consciousness was examined. METHODS Patients in a minimally conscious (MCS, n = 6) or vegetative (VS, n = 16) state and healthy controls (n = 15) were assessed. MMN and NPLOs were analyzed with single-subject, non-parametric statistics. RESULTS In 11 healthy controls and 2 VS patients, MMN was detected. More subjects showed NPLO differences in the alpha than in the theta or beta frequency ranges. In 14 healthy controls, 4 MCS patients, and 5 VS patients, lower amplitudes after deviants were found in the alpha frequency range. One healthy subject and one VS patient showed higher amplitudes after deviants. CONCLUSIONS Neither ERPs nor NPLOs could reliably distinguish MCS from VS patients. However, NPLOs were more sensitive than ERPs for detecting significantly different activity, and they possibly identified preserved processing better than ERPs. SIGNIFICANCE Intact neurophysiological attentional responses observed in the NPLOs of VS patients may indicate a need for other diagnostic techniques. Inter-individual differences in the direction of the effect should be considered as normal variance.

Altered directed functional connectivity in temporal lobe epilepsy in the absence of interictal spikes: A high density EEG study

In patients with epilepsy, seizure relapse and behavioral impairments can be observed despite the absence of interictal epileptiform discharges (IEDs). Therefore, the characterization of pathologic networks when IEDs are not present could have an important clinical value. Using Granger‐causal modeling, we investigated whether directed functional connectivity was altered in electroencephalography (EEG) epochs free of IED in left and right temporal lobe epilepsy (LTLE and RTLE) compared to healthy controls.