The perception of touch and the ventral somatosensory pathway

Preusser et al. use MRI-based lesion-symptom mapping to confirm the causal role of a ventral pathway in the perception of touch. This pathway originates downstream of the postcentral gyrus in the parietal operculum, passes the insula and the putamen, before terminating in white matter projections extending to inferior lateral prefrontal corte

Flexible Adaptive Paradigms for fMRI Using a Novel Software Package ‘Brain Analysis in Real-Time’ (BART)

In this work we present a new open source software package offering a unified framework for the real-time adaptation of fMRI stimulation procedures. The software provides a straightforward setup and highly flexible approach to adapt fMRI paradigms while the experiment is running. The general framework comprises the inclusion of parameters from subject’s compliance, such as directing gaze to visually presented stimuli and physiological fluctuations, like blood pressure or pulse. Additionally, this approach yields possibilities to investigate complex scientific questions, for example the influence of EEG rhythms or fMRI signals results themselves. To prove the concept of this approach, we used our software in a usability example for an fMRI experiment where the presentation of emotional pictures was dependent on the subject’s gaze position. This can have a significant impact on the results. So far, if this is taken into account during fMRI data analysis, it is commonly done by the post-hoc removal of erroneous trials. Here, we propose an a priori adaptation of the paradigm during the experiment’s runtime. Our fMRI findings clearly show the benefits of an adapted paradigm in terms of statistical power and higher effect sizes in emotion-related brain regions. This can be of special interest for all experiments with low statistical power due to a limited number of subjects, a limited amount of time, costs or available data to analyze, as is the case with real-time fMRI

Intermittent compared to continuous real-time fMRI neurofeedback boosts control over amygdala activation

Real-time fMRI neurofeedback is a feasible tool to learn the volitional regulation of brain activity. So far, most studies provide continuous feedback information that is presented upon every volume acquisition. Although this maximizes the temporal resolution of feedback information, it may be accompanied by some disadvantages. Participants can be distracted from the regulation task due to (1) the intrinsic delay of the hemodynamic response and associated feedback and (2) limited cognitive resources available to simultaneously evaluate feedback information and stay engaged with the task. Here, we systematically investigate differences between groups presented with different variants of feedback (continuous vs. intermittent) and a control group receiving no feedback on their ability to regulate amygdala activity using positive memories and feelings. In contrast to the feedback groups, no learning effect was observed in the group without any feedback presentation. The group receiving intermittent feedback exhibited better amygdala regulation performance when compared with the group receiving continuous feedback. Behavioural measurements show that these effects were reflected in differences in task engagement. Overall, we not only demonstrate that the presentation of feedback is a prerequisite to learn volitional control of amygdala activity but also that intermittent feedback is superior to continuous feedback presentation

Dopaminergic modulation of synaptic plasticity in the subiculum

Die Verschlüsselung und Speicherung neuer Informationen beruhen auf einer zeitgleichen Freisetzung von Dopamin (DA) in der hippokampalen Formation während der Neuigkeitserkennung. Der genaue Ort der Neuigkeitserkennung im Hippokampus (HC) ist jedoch unklar. HC und dopaminerge Projektionen des Mittelhirns bilden eine funktionelle Schleife. Aktiviert wird diese Schleife, sobald der HC neue Informationen erkennt. Entsprechend aktueller Modelle fungieren die hippokampalen Regionen, CA1 und Subikulum (SUB), als Detektor und Verteiler neuer sensorischer Informationen. Aktivitätsabhängige, synaptische Plastizität wird als einer der zellulären Mechanismen verstanden, der wesentlich den physiologischen Prozessen Lernen und Gedächtnis zugrunde liegt. Als zellulär-synaptisches Korrelat versteht man die Langzeitpotenzierung (LTP), eine langandauernde Verstärkung der synaptischen Übertragung zwischen Neuronen im HC. Die am besten untersuchte Form der LTP kann an den Synapsen der Pyramidenzellen in der CA1 Region ausgelöst werden. Trotz der Schlüsselrolle des SUB bei der Informationsübertragung ins Langzeitgedächtnis wurde bisher nicht untersucht, wie DA synaptische Plastizität in dieser Struktur moduliert. In der vorliegenden Arbeit wurde untersucht, ob und wie eine transiente Aktivierung von D1/D5-Rezeptoren (R) die Induktion einer aktivitätsabhängigen LTP in CA1, subikulären BURST und REG Pyramidenzellen bahnt. Verwendet wurde ein schwaches Stimulationsprotokoll, welches unterschwellig zur Induktion von LTP ist. Die Ergebnisse zeigen, dass zum einen eine kurzfristige D1/D5-R Aktivierung über 5-10 min LTP in beiden subikulären Neuronenarten, aber nicht in CA1 Neuronen bahnt. Zum anderen scheinen sich die Formen der induzierten LTP zwischen den subikulären Zelltypen zu unterscheiden. Es wird nachgewiesen, dass die D1/D5-R-gebahnte LTP in beiden Zellarten zwar NMDA-R-abhängig ist und die Aktivierung der Proteinkinase A benötigt. Jedoch wird in BURST Zellen die D1/D5-R-abhängige LTP stärker gebahnt als in REG Zellen, wird präsynaptisch exprimiert und beruht auf präsynaptischer Ca2+-Signalgebung. In REG Zellen dagegen ist der Expressionsort der LTP postsynaptisch lokalisiert und abhängig von der postsynaptischen Ca2+-Signalkaskade. Das Phänomen der DA-induzierten Vorbahnung einer NMDA-R-abhängigen LTP in subikulären Pyramidenzellen stimmt mit den Beobachtungen der zeitabhängigen Freisetzung von DA während der Neuigkeitserkennung in dieser Hirnregion überein und deckt einen bedeutenden Mechanismus auf, hippokampale Ausgangsinformationen zu kodieren.During novelty detection the encoding and storage of new information are based on a simultaneous release of dopamine in the hippocampcal formation. The precise location of novelty detection is yet unknown. The hippocampus and dopaminergic projections of the midbrain form a functional loop. The loop is activated when the hippocampus detects new information. According to actual models the hippocampal areas, CA1 and subiculum (SUB), act as detectors and distributers of new sensory information. Activity dependent, synaptic plasticity is known as one of the cellular mechanisms that underlies the physiological processes of learning and memory. Long-term potentiation (LTP) is recognized as a cellular-synaptic correlate, a long-lasting enhancement of synaptic transmission between neurons in the hippocampus. The most intensively investigated form of LTP can be evoked at the synapses of pyramidal neurons in area CA1. Despite the key role of the SUB in processing information to the long-term memory it is not known how dopamine modulates synaptic plasticity in this structure. In the present work it has been investigated if and how a transient activation of dopamine receptors D1/D5 primes the induction of an activity-dependent LTP in CA1, subicular burst-firing and regular-firing pyramidal cells. A weak stimulation protocol has been used which is subthreshold for inducing LTP. The results show firstly that a transient activation of D1/D5 receptors for 5-10 min primes LTP in both types of subicular neurons, but not in CA1 neurons. Secondly, the forms of induced LTP seem to differ between the subicular cell types. It is demonstrated that the LTP primed by activation of D1/D5 receptors is indeed NMDA receptor dependent and requires the activation of protein kinase A. However in burst-firing cells the D1/D5 receptor dependent LTP is stronger increased than in regular-firing cells, is expressed presynaptic and is based on presynaptic Ca2+ signaling. In regular-firing cells however, the expression of LTP is located postsynaptic and dependent on postsynaptic Ca2+ signaling. The phenomenon of dopamine induced priming of a NMDA receptor dependent LTP in subicular pyramidal cells corresponds with the observations of a time-dependent release of dopamine during novelty detection in this brain region and reveals an important mechanism of encoding hippocampal output information

Mechanisms of D1/D5 receptor-facilitated induction of subicular LTP.

<p><b>a</b>) HFS-induced, D1/D5 receptor-dependent LTP was blocked by the D1/D5 receptor antagonist SCH 23390 (0.97±0.05, <i>n</i> = 5). <b>b</b>) The NMDA receptor antagonist D-APV significantly reduced HFS-induced, D1/D5 receptor-dependent LTP (1.11±0.04, <i>p</i><0.05, <i>n</i> = 5). <b>c</b>) PKA inhibitor H-89 blocked D1/D5 receptor-facilitated LTP (1.05±0.06, <i>n</i> = 5). <b>d</b>) Summary of changes in synaptic strength as illustrated in <b>a–c</b>. One-way ANOVA revealed a significant difference between the group of SKF 38393-mediated LTP and all other groups of pharmacological intervention by comparison within last 10 minutes of recordings.</p

Stimulation site and electrophysiological properties of subicular regular-firing cells in hippocampal formation.

<p><b>a</b>) Schematic illustration of hippocampal formation with stimulating and recording electrodes in SUB. Arrows mark excitatory connections, a flash marks the stimulation site in the alveus, between CA1 and SUB. Hippocampal areas: DG  =  dentate gyrus, CA1, CA3, SUB  =  subiculum, EC  =  entorhinal cortex, sc  =  schaffer collaterals. <b>b</b>) Voltage responses upon depolarizing and hyperpolarizing current pulses. Cells discharged with single spikes, each followed by a fast afterhyperpolarization (▴). Scale bars: 25 mV, 50 ms. <b>c</b>) Expanded time scale. Initial spike frequencies and afterhyperpolarization. Scale bars: 25 mV, 10 ms. <b>d</b>) Sag (▴) and rebound potentials (▾) upon hyperpolarizing current pulses. Scale bars: 25 mV, 50 ms. <b>e</b>) Exemplary voltage response upon hyperpolarizing current pulse, illustrating calculation of sag and rebound potentials (see Methods).</p

Effect of D1/D5 receptor stimulation on synaptic and membrane properties of SUB pyramidal cells (patch-clamp).

<p>Averaged time-course of normalized EPSC amplitude under patch-clamp condition for SUB regular-firing cells before, during and after bath application of SKF 38393. No significant change in baseline transmission was observed during (min 30–40: 1.04±0.07, <i>n</i> = 6) or 20 min after application of SKF 38393 (min 30–40: 1.07±0.09).</p

Effect of D1/D5 receptor activation on synaptic and membrane properties of SUB pyramidal cells (sharp microelectrode).

<p><b>a</b>) Averaged time course of normalized EPSP amplitude, resting membrane potential (rmp) and input resistance (R_input), under sharp microelectrode condition for SUB regular-firing cells at bath application of SKF 38393. During application of SKF 38393, subicular pyramidal cells showed a transient depolarization (3.20±0.23 mV, <i>p</i><0.01, <i>n</i> = 7) that decayed to baseline level within 5 minutes after wash-out. No significant change in baseline transmission or R_input was observed during or 20 min after application of SKF 38393. rmps are expressed as differences to baseline rmp. Scale bars: 5 mV, 50 ms. <b>b</b>) Summary of D1/D5 receptor-mediated modulation of baseline transmission and passive membrane properties. Columns represent mean + SEM before (min 0–10), during (min 30–40) and after (min 50–60) application of SKF 38393.</p

Trajectories of brain remodeling in temporal lobe epilepsy.

Temporal lobe epilepsy has been usually associated with progressive brain atrophy due to neuronal cell loss. However, recent animal models demonstrated a dual effect of epileptic seizures with initial enhancement of hippocampal neurogenesis followed by abnormal astrocyte proliferation and neurogenesis depletion in the chronic stage. Our aim was to test for the hypothesized bidirectional pattern of epilepsy-associated brain remodeling in the context of the presence and absence of mesial temporal lobe sclerosis. We acquired MRIs from a large cohort of mesial temporal lobe epilepsy patients with or without hippocampus sclerosis on radiological examination. The statistical analysis tested explicitly for common and differential brain patterns between the two patients' cohorts and healthy controls within the computational anatomy framework of voxel-based morphometry. The main effect of disease was associated with continuous hippocampus volume loss ipsilateral to the seizure onset zone in both temporal lobe epilepsy cohorts. The post hoc simple effects tests demonstrated bilateral hippocampus volume increase in the early epilepsy stages in patients without hippocampus sclerosis. Early age of onset and longer disease duration correlated with volume decrease in the ipsilateral hippocampus. Our findings of seizure-induced hippocampal remodeling are associated with specific patterns of mesial temporal lobe atrophy that are modulated by individual clinical phenotype features. Directionality of hippocampus volume changes strongly depends on the chronicity of disease. Specific anatomy differences represent a snapshot within a progressive continuum of seizure-induced structural remodeling

Activation of D1/D5 receptors facilitates the induction of LTP in SUB regular-firing cells.

<p><b>a</b>) To investigate the facilitation of LTP by the D1/D5 receptor agonist SKF 38393, a brief HFS protocol was used (arrow, also see Methods), which was insufficient to induce LTP under control conditions (1.03±0.04, <i>n</i> = 10). HFS given 5 minutes after application of SKF 38393 induced a robust LTP in SUB regular-firing cells (1.53±0.08, <i>p</i><0.001, <i>n</i> = 7). EPSPs were recorded before (1) and after HFS (2,3). Scale bars: 5 mV, 50 ms. <b>b</b>) Summary of SKF 38393-induced effects on LTP induction in SUB regular-firing neurons.</p