Reduction In Neural Activity Research Articles

Sustained happiness? Lack of repetition suppression in right-ventral visual cortex for happy faces

Emotional stimuli have been shown to preferentially engage initial attention but their sustained effects on neural processing remain largely unknown. The present study evaluated whether emotional faces engage sustained neural processing by examining the attenuation of neural repetition suppression to repeated emotional faces. Repetition suppression of neural function refers to the general reduction of neural activity when processing a repeated stimulus. Preferential processing of emotional face stimuli, however, should elicit sustained neural processing such that repetition suppression to repeated emotional faces is attenuated relative to faces with no emotional content. We measured the reduction of functional magnetic resonance imaging signals associated with immediate repetition of neutral, angry and happy faces. Whereas neutral faces elicited the greatest suppression in ventral visual cortex, followed by angry faces, repetition suppression was the most attenuated for happy faces. Indeed, happy faces showed almost no repetition suppression in part of the right-inferior occipital and fusiform gyri, which play an important role in face-identity processing. Our findings suggest that happy faces are associated with sustained visual encoding of face identity and thereby assist in the formation of more elaborate representations of the faces, congruent with findings in the behavioral literature.

Affect Regulation and Pain in Borderline Personality Disorder: A Possible Link to the Understanding of Self-Injury

Patients with borderline personality disorder (BPD) experience intense emotions and often show a deficiency of emotion regulation skills. Moreover, they display high prevalence rates of self-injurious behavior. Patients report engaging in self-injurious behavior due to its immediate relief effects of emotional tension. Pain in BPD has further been observed to lead to a reduction in neural activity in the amygdala and anterior cingulate cortex, which may be attributed to patients' perception of relaxation. To investigate the potential role of self-inflicted pain as a means of affect regulation in patients with BPD, we conducted a functional magnetic resonance imaging study using picture stimuli to induce negative (vs. neutral) affect and thermal stimuli to induce heat pain (vs. warmth perception). The painful heat stimuli were administrated at an individual temperature for each subject. Twenty patients with BPD and 23 healthy control subjects were included in the study. Both negative and neutral pictures led to stronger activation of the amygdala, insula, and anterior cingulate cortex in patients with BPD than in healthy control subjects. Amygdala activation correlated with self-reported deficits in emotion regulation. During the sensory stimulation, we found decreased amygdala and anterior cingulate cortex activation, which was independent of painfulness. The results are in line with previous findings on emotional hyperactivity in BPD and suggest that pain stimuli in BPD are processed differently depending on the arousal status. Finally, we can preliminarily support the idea of a general mechanism of attentional shift underlying the soothing effect of pain in BPD.

Too much of a good thing: Long-term treatment with salicylate strengthens outer hair cell function but impairs auditory neural activity

Aspirin has been extensively used in clinical settings. Its side effects on auditory function, including hearing loss and tinnitus, are considered as temporary. A recent promising finding is that chronic treatment with high-dose salicylate (the active ingredient of aspirin) for several weeks enhances expression of the outer hair cell (OHC) motor protein (prestin), resulting in strengthened OHC electromotility and enhanced distortion product otoacoustic emissions (DPOAE). To follow up on these observations, we carried out two studies, one planned study of age-related hearing loss restoration and a second unrelated study of salicylate-induced tinnitus. Rats of different strains and ages were injected with salicylate at a dose of 200 mg/kg/day for 5 days per week for 3 weeks or at higher dose levels (250–350 mg/kg/day) for 4 days per week for 2 weeks. Unexpectedly, while an enhanced or sustained DPOAE was seen, permanent reductions in the amplitude of the cochlear compound action potential (CAP) and the auditory brainstem response (ABR) were often observed after the chronic salicylate treatment. The mechanisms underlying these unexpected, permanent salicylate-induced reductions in neural activity are discussed.

Object repetition leads to local increases in the temporal coordination of neural responses

Experience with visual objects leads to later improvements in identification speed and accuracy (“repetition priming”), but generally leads to reductions in neural activity in single-cell recording studies in animals and fMRI studies in humans. Here we use event-related, source-localized MEG (ER-SAM) to evaluate the possibility that neural activity changes related to priming in occipital, temporal, and prefrontal cortex correspond to more temporally coordinated and synchronized activity, reflected in local increases in the amplitude of low-frequency activity fluctuations (i.e. evoked power) that are time-locked to stimulus onset. Subjects (N = 17) identified pictures of objects that were either novel or repeated during the session. Tests in two separate low-frequency bands (theta/alpha: 5–15 Hz; beta: 15–35 Hz) revealed increases in evoked power (5–15 Hz) for repeated stimuli in the right fusiform gyrus, with the earliest significant increases observed 100–200 ms after stimulus onset. Increases with stimulus repetition were also observed in striate/extrastriate cortex (15–35 Hz) by 200–300 ms post-stimulus, along with a trend for a similar pattern in right lateral prefrontal cortex (5–15 Hz). Our results suggest that experience-dependent reductions in neural activity may affect improved behavioral identification through more coordinated, synchronized activity at low frequencies, constituting a mechanism for more efficient neural processing with experience.

Repetitive transcranial magnetic stimulation improve tinnitus in normal hearing patients: a double‐blind controlled, clinical and neuroimaging outcome study

Tinnitus is a frequent disorder which is very difficult to treat and there is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Targeted modulation of tinnitus-related cortical activity has been proposed as a promising new treatment approach. We aimed to investigate both immediate and long-term effects of low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) in patients with tinnitus and normal hearing. Using a parallel design, 20 patients were randomized to receive either active or placebo stimulation over the left temporoparietal cortex for five consecutive days. Treatment results were assessed by using the Tinnitus Handicap Inventory. Ethyl cysteinate dimmer-single photon emission computed tomography (SPECT) imaging was performed before and 14 days after rTMS. After active rTMS there was significant improvement of the tinnitus score as compared to sham rTMS for up to 6 months after stimulation. SPECT measurements demonstrated a reduction of metabolic activity in the inferior left temporal lobe after active rTMS. These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus, by demonstrating a significant reduction of tinnitus complaints over a period of at least 6 months and significant reduction of neural activity in the inferior temporal cortex, despite the stimulation applied on the superior temporal cortex.

Dissociation of Neural Mechanisms Underlying Orientation Processing in Humans

Orientation selectivity is a fundamental, emergent property of neurons in early visual cortex, and the discovery of that property has dramatically shaped how we conceptualize visual processing. However, much remains unknown about the neural substrates of this basic building block of perception, and what is known primarily stems from animal physiology studies. To probe the neural concomitants of orientation processing in humans, we employed repetitive transcranial magnetic stimulation (rTMS), which can significantly attenuate neuronal spiking activity, hemodynamic responses, and local field potentials within a focused cortical region. Using rTMS to suppress neural responses evoked by stimuli falling within a local region of the visual field, we were able to dissociate two distinct components of the neural circuitry underlying orientation processing: selectivity and contextual effects. Orientation selectivity gauged by masking was unchanged by rTMS, whereas an otherwise robust orientation repulsion illusion was weakened after rTMS. This dissociation implies that orientation processing in humans relies on distinct mechanisms, only one of which was impacted by rTMS. These results are consistent with models positing that orientation selectivity is governed by patterns of convergence of thalamic afferents onto cortical neurons, with intracortical activity then shaping population responses amongst those cortical neurons.

Age-related changes in neural activity associated with familiarity, recollection and false recognition

Older adults often exhibit elevated false recognition for events that never occurred, while simultaneously experiencing difficulty in recognizing events that actually occurred. It has been proposed that reduced recollection in conjunction with an over-reliance on familiarity may contribute to this pattern of results. This explanation is somewhat inconsistent, however, with recent evidence suggesting that familiarity and associated neural activity are reduced in healthy aging. Alternatively, given that illusory memory may be based, in part, on veridical memory processes (recollection/familiarity), one might predict that older adults exhibit enhanced false alarm rates because the neural signatures associated with true recognition (hits) and false recognition (false alarms) are less distinguishable in old than in young adults. Here, we used event-related fMRI to measure the effects of aging on neural activity associated with recollection, familiarity and familiarity-based false alarms for objects in young and older adults. Compared to young adults, older adults exhibited elevated false alarm rates and impaired behavioral indices of recollection and familiarity. Imaging data showed that older adults exhibited reduced recollection effects in the left parietoccipital cortex. Furthermore, while similar regions in frontal, parietal, lateral and inferior temporal cortices contributed to familiarity-based true and false recognition, reduced familiarity-related activity in frontal and inferior temporal regions in the older adults resulted in decreased differentiation between true and false recognition effects in this group. Our results suggest that reductions in neural activity associated with both recollection and familiarity for studied items may contribute to elevated false recognition in older adults, via reduced differentiation between the neural activity associated with true and false memory.

Repetition suppression and reactivation in auditory-verbal short-term recognition memory.

The neural response to stimulus repetition is not uniform across brain regions, stimulus modalities, or task contexts. For instance, it has been observed in many functional magnetic resonance imaging (fMRI) studies that sometimes stimulus repetition leads to a relative reduction in neural activity (repetition suppression), whereas in other cases repetition results in a relative increase in activity (repetition enhancement). In the present study, we hypothesized that in the context of a verbal short-term recognition memory task, repetition-related “increases” should be observed in the same posterior temporal regions that have been previously associated with “persistent activity” in working memory rehearsal paradigms. We used fMRI and a continuous recognition memory paradigm with short lags to examine repetition effects in the posterior and anterior regions of the superior temporal cortex. Results showed that, consistent with our hypothesis, the 2 posterior temporal regions consistently associated with working memory maintenance, also show repetition increases during short-term recognition memory. In contrast, a region in the anterior superior temporal lobe showed repetition suppression effects, consistent with previous research work on perceptual adaptation in the auditory–verbal domain. We interpret these results in light of recent theories of the functional specialization along the anterior and posterior axes of the superior temporal lobe.

The dynamic mechanisms of placebo induced analgesia: Evidence of sustained and transient regional involvement

Previously, we demonstrated that placebo analgesia (PA) accompanies reductions in neural activity during painful stimulation. This study investigated areas of the brain where the neural activity was increased during PA. The literature has associated PA with two potential mechanisms of action; one sustained (e.g., engaged for the duration of PA), the other, transitory (e.g., a feedback mechanism). We propose that PA results from the engagement of two complementary pain-modulation mechanisms that are identified with fMRI data as a main effect for condition or a time ∗ condition interaction. The mechanism with sustained activity should activate the emotional regulation circuitry needed for memory formation of the event. The mechanism with transient activity should process cognitive and evaluative information of the stimuli in the context of the placebo suggestion to confirm the expectations set by it. To identify regions involved with these mechanisms, we re-analyzed fMRI data from two conditions: baseline (B) and PA. Results support the presence of both mechanisms, identified as two neural-networks with different temporal characteristics. Regions with sustained activity primarily involved the temporal and parahippocampal cortices. Conversely, brain regions with transient activity included linguistic centers in the left hemisphere and frontal regions of the right hemisphere generally associated with executive functioning. Together, these mechanisms likely engage analgesic processes and then simply monitor the system for unexpected stimuli, effectively liberating resources for other processes. Identifying brain regions associated with pain-modulation with different temporal profiles is consistent with the multidimensionality of PA and highlights the need for continued investigation of this construct.

Modifications of the interactions in the motor networks when a movement becomes automatic

A crucial feature of the motor system is the ability to control some movements automatically. We have previously shown that all parts of the motor networks reduce their activity with automaticity, and, while this change may indicate increased efficiency in terms of neural processing, it is not clear how motor skill can be maintained after a reduction of neural activity. In the current study, we used functional MRI (fMRI) to investigate influences on the effective connectivity of the brain motor networks when movements become automatic. Subjects practiced a sequential movement until they could execute it automatically, and task-related brain fMRI activation was measured before and after they achieved automaticity. Using the psychophysiological interaction (PPI) method, we found that the cerebellum, cingulate motor area, supplementary motor area, and putamen had significantly greater connectivity, whereas the precuneus had less connectivity in the motor networks at the automatic stage. Our findings demonstrate that the importance of the attention networks decrease when movements become automatic. Moreover, the process of automaticity is accompanied by a strengthened interaction of central motor networks even though the magnitude of the activation is decreased. We speculate that this increase in connectivity reflects more efficient neural coding of movement at the automatic stage.

Efficient motor control: how can less be more?

The results of a scientific study sometimes surprise us, and at other times comfort us. Such reactions reflect the framework of expectations we had before the study was carried out. This framework ideally summarizes our shared prior knowledge and makes new results seem more or less plausible in light of that knowledge. In the present issue of The Journal of Physiology, Wu et al. (2008) report a comforting result. When a new motor task is practiced to the point that subjects can perform it automatically, that is, without degradation of performance when a second task is concurrently carried out, a group of motor areas in the brain become more strongly connected. The same authors had previously shown that when a movement is practiced until it becomes automatic, a major change in brain activation pattern is a reduction of neural activity in task-related areas (Wu et al. 2004). That is, as movement guidance changes from a ‘novice’ mode, requiring attention, to an automatic mode, there is no qualitative change in the pattern of brain activation: the same areas are activated by the task before and after practice. However, these areas become able to control the same movements with a reduced amount of activation. This was (or at least should have been) a surprising result. It might be tempting to interpret reduction of activation as the neural equivalent of subtraction of task components: activity before practice = attention + motor control; reduced activity after practice = motor control alone. However, there is a paradox in this interpretation. If the difference in brain activity reflected only a difference in attention, this would imply that the portion of activity responsible for motor control is the same before and after practice. But then how can motor control after practice be resistant to distraction by a concurrent task? In order for automaticity to have arisen, the neural substrate responsible for controlling the movement must have changed: if the same movements are now resistant to interference by a simultaneous second task, they must be guided by a different motor control strategy, with a presumably different neural code. How could a reduction of activation in motor areas be responsible for the radical change in the nature of motor control associated with automatic execution? The answer provided by Wu et al. in the present study resolves this paradox, and is reassuring at three levels. First, the authors identified a change in functional connectivity among motor areas associated with the development of automaticity. This finding reassures us that the neural substrate responsible for automatic motor control is indeed different from that responsible for novice performance. Second, the change identified is of the type we have come to expect, ever since Donald Hebb's postulate (Hebb, 1949), to be associated with learning: if a movement must be practiced in order to become automatic, then learning must occur, and thus synaptic strengths must change. Third, the combined findings of Wu et al.'s original (Wu et al. 2004) and present studies, are evidence of an increase in neural efficiency: the combination of reduction of activation and strengthening of functional connectivity suggests a more efficient neural code for controlling a given task. Neural efficiency has long been investigated in relationship to human intelligence (Vernon, 1993), but these studies have been fraught with the long list of potential confounding factors (task complexity, use of strategy, past experience) associated with the study of such a complex measure of nervous system function. A task as simple as tapping fingers in a sequence, when combined with analysis not only of brain activation patterns, but also of functional connectivity, offers a more easily controlled system for investigating concepts like neural efficiency. By presenting evidence of increased neural efficiency in the automatic performance of movement sequences, Wu et al. have brought an exciting new level of detail to our understanding of the neural code underlying movement.

An fMRI study of subliminal priming of spoken words

Repetition priming has been widely used to study spoken and written word recognition. Its physiological counterpart is repetition suppression, a reduction in neural activity resulting in a measurable decrease of the fMRI signal. By varying the representational level at which the repetition occurs, one can determine which properties are encoded in a given brain area, and which are not. We will report on an fMRI experiment using subliminal auditory priming of spoken words. Subliminal priming has been used, for example, by Dehaene et al. to study visual word recognition. Our experiment employs a technique developped by Kouider & Dupoux that allows subliminal presentation of auditory stimuli using temporal compression and forward masking. The participants perform a lexical decision task on the target item, which is preceded by a subliminal prime that can be phonetically identical or different from the target, and spoken or not by the same speaker. A fast-event related paradigm is used where each prime-target pair is presented during silent gaps between the acquisitions. The planned analyses will seek to identify the brain regions showing subliminal repetition suppression to word repetition regardless of speaker change, as well as other areas sensitive to speaker change regardless of linguistic content.

The Barista on the Bus: Cellular and Synaptic Mechanisms for Visual Recognition Memory

Our ability to recognize that something is familiar, often referred to as visual recognition memory, has been correlated with a reduction in neural activity in the perirhinal cortex. In this issue of Neuron, Griffiths et al. now provide evidence that this form of memory requires AMPA receptor endocytosis and long-term depression of excitatory synapses in this brain area.

Oblique effects beyond low-level visual processing

A number of studies have demonstrated a reduction in neural activity for oblique gratings as compared to horizontal or vertical gratings. This has been associated with the psychophysical oblique effect. Using event-related potentials, we now assessed the neural activity associated with the processing of higher-order stimuli of different orientations. We applied a novel stimulus paradigm that is particularly suited to investigate mid- and high-level vision by obviating low-level responses. It consisted of a line grid that emerged perspicuously from a continuous movement of stimulus elements without any temporal discontinuances in stimulus presentation. This Gestalt could be oriented along the cardinal axes or rotated by 45°. We obtained distinct event-related potentials with a moderate task-dependence. They showed a correlate of Gestalt processing that did not depend on the orientation, followed by a P300-like component that was 50% larger for the 45° Gestalt. Surprisingly, this oblique effect is opposite to previous studies using gratings. We propose that it originated from a bias in neural processing, induced by the long-term environmental experience of the subjects.

Neural correlates of priming on occluded figure interpretation in human fusiform cortex

Event Abstract Back to Event Neural correlates of priming on occluded figure interpretation in human fusiform cortex Lichan Liu1, 2*, G. Plomp3, 4, C. Van Leeuwen3 and Andreas A. Ioannides1, 2 1 Lab for Human Brain Dynamics (LHBD), RIKEN Brain Science Institute (BSI), Japan 2 LHBD, 33 Arch Makarios III Avenue, Cyprus 3 Lab for Perceptual Dynamics, RIKEN BSI, Japan 4 Lab of Psychophysics, Brain Mind Institute, EPFL, Switzerland The visual system rapidly completes a partially occluded figure. We probed the completion process by using priming in combination with neuroimaging techniques. Priming leads to more efficient visual processing and thus a reduction in neural activity in relevant brain areas. These areas were studied with high spatial resolution and temporal accuracy with focus on early perceptual processing. We recorded magnetoencephalographic (MEG) responses from 10 human volunteers in a primed same–different task for test figures. The test figures were preceded by a sequence of two figures, a prime or control figure followed by an occluded figure. The prime figures were one of three possible interpretations of the occluded figures: global and local completions and mosaic interpretation. A significant priming effect showing the processing of the composite figure is biased by the preceding first stimulus was evident: in primed trials as compared with control trials, subjects responded faster and the latency was shorter in the MEG signal for the largest peak between 50 and 300 ms after the occluded figure onset. To ensure accurate anatomical definition in our interrogation of the data, we used statistical parametric mapping in conjunction with magnetic field tomography (MFT) to characterize responses at all points in peristimulus time throughout the brain. Having identified regionally specific visual evoked responses we looked at the significance of the priming related effects in these areas. Notably, we found significantly reduced activity in the right fusiform cortex between 120 and 200 ms after composite figure onset in primed as compared with control trials (See Figure). Thus we localized the effect of priming on the perceptual interpretation of occluded figures in the right fusiform cortex. This applied to all alternative figure interpretations under investigation, global and local completions as well as mosaic interpretation [1]. In a separate analysis of the MEG signal we identified a stronger peak with a slightly earlier latency for the evoked response of the second composite figure when it was preceded by mosaic as compared with either local or global first figures [2]. liu tn_liu

Hyperphosphorylated tau in parahippocampal cortex impairs place learning in aged mice expressing wild-type human tau

To investigate how tau affects neuronal function during neurofibrillary tangle (NFT) formation, we examined the behavior, neural activity, and neuropathology of mice expressing wild-type human tau. Here, we demonstrate that aged (>20 months old) mice display impaired place learning and memory, even though they do not form NFTs or display neuronal loss. However, soluble hyperphosphorylated tau and synapse loss were found in the same regions. Mn-enhanced MRI showed that the activity of the parahippocampal area is strongly correlated with the decline of memory as assessed by the Morris water maze. Taken together, the accumulation of hyperphosphorylated tau and synapse loss in aged mice, leading to inhibition of neural activity in parahippocampal areas, including the entorhinal cortex, may underlie place learning impairment. Thus, the accumulation of hyperphosphorylated tau that occurs before NFT formation in entorhinal cortex may contribute to the memory problems seen in Alzheimer's disease (AD).

Sustained Neural Activity Patterns during Working Memory in the Human Medial Temporal Lobe

In contrast to classical findings that the medial temporal lobe (MTL) specifically underlies long-term memory, previous data suggest that MTL structures may also contribute to working memory (WM). However, the neural mechanisms by which the MTL supports WM have remained unknown. Here, we exploit intracranial EEG to identify WM-specific sustained activity patterns with the highest temporal and spatial resolution currently available in humans. Using a serial Sternberg paradigm, we found a positive shift of the direct current (DC) potential and a long-lasting decrease in MTL gamma-band activity during maintenance of a single item, reflective of a sustained reduction in neural activity. Maintenance of an increasing number of items elicited an incrementally negative shift of the DC potential and an increase in MTL gamma-band activity. In addition, the paradigm was conducted in healthy control subjects using functional magnetic resonance imaging. This confirmed that our results were not caused by pathological processes within the MTL, and that this region was indeed specifically activated during the task. Our results thus provide direct evidence for sustained neural activity patterns during working memory maintenance in the MTL, and show that these patterns depend on WM load.

Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients

Previous experiments found that placebos produced small decreases in neural activity of pain-related areas of the brain, yet decreases were only statistically significant after termination of stimuli and in proximity to when subjects rated them. These changes could reflect report bias rather than analgesia. This functional magnetic resonance imaging (fMRI) study examined whether placebo analgesia is accompanied by reductions in neural activity in pain-related areas of the brain during the time of stimulation. Brain activity of irritable bowel syndrome patients was measured in response to rectal distension by a balloon barostat. Large reductions in pain and in brain activation within pain-related regions (thalamus, somatosensory cortices, insula, and anterior cingulate cortex) occurred during the placebo condition. Results indicate that decreases in activity were related to placebo suggestion and a second factor (habituation/attention/conditioning). Although many factors influence placebo analgesia, it is accompanied by reduction in pain processing within the brain in clinically relevant conditions.

Selective and Quickly Reversible Inactivation of Mammalian Neurons In Vivo Using the Drosophila Allatostatin Receptor

Genetic strategies for perturbing activity of selected neurons hold great promise for understanding circuitry and behavior. Several such strategies exist, but there has been no direct demonstration of reversible inactivation of mammalian neurons in vivo. We previously reported quickly reversible inactivation of neurons in vitro using expression of the Drosophila allatostatin receptor (AlstR). Here, adeno-associated viral vectors are used to express AlstR in vivo in cortical and thalamic neurons of rats, ferrets, and monkeys. Application of the receptor's ligand, allatostatin (AL), leads to a dramatic reduction in neural activity, including responses of visual neurons to optimized visual stimuli. Additionally, AL eliminates activity in spinal cords of transgenic mice conditionally expressing AlstR. This reduction occurs selectively in AlstR-expressing neurons. Inactivation can be reversed within minutes upon washout of the ligand and is repeatable, demonstrating that the AlstR/AL system is effective for selective, quick, and reversible silencing of mammalian neurons in vivo.

(887): Placebo analgesia is accompanied by active afferent inhibition during painful stimulation

Previous experiments found that placebos produced small decreases in neural activity of pain-related areas of the brain, yet decreases were only statistically significant after termination of stimuli and in proximity to when subjects rated them. These changes could reflect report bias rather than analgesia. A brain imaging study examined whether placebo analgesia is accompanied by reductions in neural activity in pain-related areas of the brain during the time of stimulation. Brain activity of irritable bowel syndrome patients was measured in response to rectal distension by a balloon barostat.