Subcortical Activity Research Articles

Coding of Incisional Pain in the Brain

In this study, the activation of different brain areas after an experimental surgical incision was assessed by functional magnetic resonance imaging, and the pathophysiological role of distinct brain activation patterns for pain perception after incision was analyzed. Thirty male volunteers (mean age +/-SD, 25+/- 5 yr) received an experimental incision (4 mm) within the volar aspect of the right forearm using a ceramic scalper blade, and 14 volunteers (mean age +/- SD, 25 +/- 4 yr) received a sham procedure. Magnetic resonance images were taken before, during (0-2 min), and after incision or sham procedure (2-4.5, 4.5-10, 24-29, and 44-49 min) at a 3T scanner using a block design. Subjective pain ratings by a numerical pain scale were performed between the scans. Functional magnetic resonance imaging analysis showed a distinct temporal profile of activity within specific brain regions during and after the injury. Lateralization (predominantly contralateral to the incision) and increased brain activity of the somatosensory cortex, frontal cortex, and limbic system were observed in subjects after incision, when compared with individuals receiving sham procedure. Peak brain activation occurred about 2 min after incision and decreased subsequently. A distinct correlation between evoked pain ratings and brain activity was observed for the anterior cingulate cortex, insular cortex, thalamus, frontal cortex, and somatosensory cortex. These findings show different and distinct cortical and subcortical activation patterns over a relevant time period after incision. Pain sensitivity hereby has an influence on the activity profile. This may have important implications for encoding ongoing pain after a tissue injury, for example, resting pain in postoperative patients.

Cognitive mapping through electrophysiology

Cognitive mapping through electrophysiology

Sex Differences in Stress Response Circuitry Activation Dependent on Female Hormonal Cycle

Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this functional magnetic resonance imaging study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry [amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and anterior cingulate gyrus (ACG)]. Women were scanned twice based on normal variation in menstrual cycle hormones [i.e., early follicular (EF) compared with late follicular-midcycle (LF/MC) menstrual phases]. Using SPM8b, there were few significant differences in blood oxygenation level-dependent (BOLD) signal changes in men compared to EF women, except ventromedial nucleus (VMN), lateral hypothalamic area (LHA), left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males.

Dopaminergic Impact on Cortical Excitability in Humans

Dopamine is a major neuromodulatory agent of the central nervous system. The neurotransmitter has a non-linear dose-dependent effect on cortical excitability and activity, which depends on spontaneous activity, dopamine concentration, and dopaminergic sub-receptors, amongst others. By its impact on cortical and subcortical network activity and excitability, dopamine modulates such cognitive performance as attention, as well as learning and memory formation. Although animal studies have enhanced our knowledge about the physiology of dopamine considerably, the transferability of the results to conscious humans is limited due to altered spontaneous neuronal activity in anesthetized animals or slice experiments. Recently emerged noninvasive brain stimulation techniques enable the exploration of cortical excitability in humans. Here we review the respective experimental results and derive conclusions about how dopamine might affect the cortical excitability of the human brain.

Processed electroencephalogram in depth of anesthesia monitoring

We critically review the principles underlying processed electroencephalogram (EEG) monitors and recent studies validating their use in monitoring anesthetic depth. Depth of anesthesia is a theoretical construct to conceptualize anesthetic effects on the central nervous system as discrete or continuous phases or states. Clinical signs for assessing anesthetic depth are currently being supplemented by brain monitors. Their use may help to prevent insufficient anesthesia, which can lead to intraoperative awareness with recall, as well as anesthetic overdose, which may be associated with adverse events. Commercial and open-source brain monitoring indices are computed from frequency, entropy, or information theoretic analysis of the spontaneous or evoked EEG. These techniques are undergoing refinement to determine the best method for titrating anesthetics. Future depth-of-anesthesia monitors will benefit from current work aimed at correlating anesthetic effects to alterations in specific neural circuits. Current processed EEG monitors are limited by their calibration range and the interpatient variability in their dose-response curves. The next generation of depth-of-anesthesia monitors will require a greater understanding of the transformations of cortical and subcortical activity into EEG signals, the effects of anesthetics at a systems level, and the neural correlates of consciousness.

Minimizing the Risks of Sudden Infant Death Syndrome: To Swaddle or Not to Swaddle?

To evaluate the effects of swaddling on infant arousability, particularly the progression of subcortical activation (SCA) to full cortical arousal (CA), because impaired arousal may contribute to sudden infant death syndrome. Healthy term infants, who were routinely swaddled (n = 15) or unswaddled (n = 12) at home, were studied with daytime polysomnography at 3 to 4 weeks and 3 months after birth. When both swaddled and unswaddled, arousability was assessed with a pulsatile jet of air at the nostrils. Larger increases in overall arousal thresholds (SCA plus CA) with swaddling were observed in infants who were easiest to arouse when unswaddled. Swaddling did not alter SCA or CA frequencies of routinely swaddled infants at either age. In infants who were naïve to swaddling, arousal thresholds were increased and CA frequency decreased during swaddled quiet sleep at 3 months. This study provides a scientific basis for assessing the safety of swaddling in infant care practice. The decreased cortical arousals observed in infants unfamiliar with swaddling may correspond to the increased risk of sudden infant death syndrome for inexperienced prone sleepers.

Levodopa-induced striatal activation in Parkinson's disease: A functional MRI study

Objective To assess the effect of a single levodopa dose (200 mg levodopa, 50 mg carbidopa = sdLD) on cortical and subcortical motor-circuit activation during bimanual grip force in patients with Parkinson's disease (PD). Patients and methods We studied 12 right-handed patients with PD (Hoehn–Yahr stages I–II) after a period of at least 12 h without medication (OFF state) and a second time 1 h after oral administration of sdLD (ON state) using functional magnetic resonance imaging (fMRI). Blood-oxygenation-level-dependency (BOLD) fMRI was measured while participants underwent two unilateral and two bimanual grip force movements with a defined movement amplitude and force (10 N) in a block design. 12 age matched healthy subjects were studied as controls (without administration of sdLD). Results Bimanual grip force tasks activated a specific pattern of cortical and subcortical structures in all patients during the OFF state and after levodopa administration with statistically significant differences in putamen and thalamus comparing the OFF and ON condition. In contrast, no such significant changes were observed in cortical structures. Between-group analysis revealed higher putaminal activity in controls compared to OFF state in bimanual tasks, while these differences disappeared after administration of levodopa. Conclusions Our results indicate that the putamen and thalamus are the regions within the cortico-subcortical motor-circuit with most prominent response to levodopa. In our study, cortical motor areas did not respond to levodopa as one could have expected from previous studies. These findings contribute to the increasing evidence that an extended model of the underlying pathophysiology of motor dysfunctions in PD is warranted.

Functional reorganization in the brain afar contralateral C7 transfer to the median nerve

Objective To investigate changes in brain function zones following contralateral Co transfer and its possible mechanisms, and provide scientific bases for clinical measurements to improve functional recovery after such nerve transfer. Methods Experiment al group: 6 adult male patients with left brachial plexus total avulsions who underwent contralateral G7 transfer and had recovered M3 or above muscle power of wrist flexors and finger flexors on the injured side under volitional vigorous healthy shoulder (right side) adduction. Control group:6 healthy male adults whose motor task was w adduct the right shoulder. Positron Emission tomography (PET) techniques were applied to acquire scans of the brain for analysis. Results PEI scans showed excitation mainly in the left hemisphere upon right shoulder adduction in the control group. In the experimental group, in addition to excitation in the left hemisphere, right shoulder adduction resulted in excitation in the right frontal lobe and apical lobe, including SMI and SMA, with simultaneous subcortical area activation. Conclusion Functional imaging evidences of transhemispheric plasticity in adult brain were obtained. The cortical areas involved in functional reorganization were delineated. The hypothesis that the brain may try to restore control of an injured limb to its original cortical areas after nerve transfer was put forth. Key words: Nerve transfer; Brachial plexus; Neuronal plasticity; Somatosensory cortex

The neural correlates of social attention: automatic orienting to social and nonsocial cues

Previous evidence suggests that directional social cues (e.g., eye gaze) cause automatic shifts in attention toward gaze direction. It has been proposed that automatic attentional orienting driven by social cues (social orienting) involves a different neural network from automatic orienting driven by nonsocial cues. However, previous neuroimaging studies on social orienting have only compared gaze cues to symbolic cues, which typically engage top-down mechanisms. Therefore, we directly compared the neural activity involved in social orienting to that involved in purely automatic nonsocial orienting. Twenty participants performed a spatial cueing task consisting of social (gaze) cues and automatic nonsocial (peripheral squares) cues presented at short and long stimulus (cue-to-target) onset asynchronies (SOA), while undergoing fMRI. Behaviorally, a facilitation effect was found for both cue types at the short SOA, while an inhibitory effect (inhibition of return: IOR) was found only for nonsocial cues at the long SOA. Imaging results demonstrated that social and nonsocial cues recruited a largely overlapping fronto-parietal network. In addition, social cueing evoked greater activity in occipito-temporal regions at both SOAs, while nonsocial cueing recruited greater subcortical activity, but only for the long SOA (when IOR was found). A control experiment, including central arrow cues, confirmed that the occipito-temporal activity was at least in part due to the social nature of the cue and not simply to the location of presentation (central vs. peripheral). These results suggest an evolutionary trajectory for automatic orienting, from predominantly subcortical mechanisms for nonsocial orienting to predominantly cortical mechanisms for social orienting.

Maternal smoking impairs arousal patterns in sleeping infants.

Impairment of the arousal process from sleep is thought to be involved in the pathogenesis of sudden infant death syndrome (SIDS). We hypothesized that a greater propensity for cortical arousal in the prone position may, in a normal infant, be a protective mechanism to promote complete arousal in a vulnerable sleeping position, a protection that is absent in SIDS victims. We aimed to examine the arousal process in a group of infants exposed to maternal smoking, who are thus at higher risk for SIDS. Twelve healthy, full-term infants born to smoking mothers were studied using daytime polysomnography at 2 to 4 weeks, 2 to 3 months and 5 to 6 months postnatal age. Data were compared with 13 healthy infants born to nonsmoking mothers. Arousal was induced by pulsatile air-jet stimulation to the nostrils during active and quiet sleep, in both supine and prone positions. For each stimulus, physiologic and electroencephalogram changes were visually assessed and arousal responses were classified as sub-cortical activation or cortical arousal. In smoke-exposed infants, the progression from sub-cortical activation to cortical arousal was depressed at 2 to 4 weeks and 5 to 6 months. There was no effect of maternal smoking observed at 2 to 3 months; however, a significant dose-dependent relationship between cortical activation proportions and urinary cotinine levels was present in both supine and prone positions. We have shown that maternal smoking is associated with impaired arousal processes to trigeminal stimulation that may increase the risk for SIDS. This further highlights the importance of public education of the risks of maternal smoking.

Gamma activity and reactivity in human thalamic local field potentials

Depth recordings in patients with Parkinson's disease on dopaminergic therapy have revealed a tendency for oscillatory activity in the basal ganglia that is sharply tuned to frequencies of approximately 70 Hz and increases with voluntary movement. It is unclear whether this activity is essentially physiological and whether it might be involved in arousal processes. Here we demonstrate an oscillatory activity with similar spectral characteristics and motor reactivity in the human thalamus. Depth signals were recorded in 29 patients in whom the ventral intermediate or centromedian nucleus were surgically targeted for deep brain stimulation. Thirteen patients with four different pathologies showed sharply tuned activity centred at approximately 70 Hz in spectra of thalamic local field potential (LFP) recordings. This activity was modulated by movement and, critically, varied over the sleep-wake cycle, being suppressed during slow wave sleep and re-emergent during rapid eye movement sleep, which physiologically bears strong similarities with the waking state. It was enhanced by startle-eliciting stimuli, also consistent with modulation by arousal state. The link between this pattern of thalamic activity and that of similar frequency in the basal ganglia was strengthened by the finding that fast thalamic oscillations were lost in untreated parkinsonian patients, paralleling the behaviour of this activity in the basal ganglia. Furthermore, there was sharply tuned coherence between thalamic and pallidal LFP activity at approximately 70 Hz in eight out of the 11 patients in whom globus pallidus and thalamus were simultaneously implanted. Subcortical oscillatory activity at approximately 70 Hz may be involved in movement and arousal.

68. Cortical and subcortical motor activity in patients with sporadic ALS studied with fMRI

68. Cortical and subcortical motor activity in patients with sporadic ALS studied with fMRI

P02-20 Self-reported rumination as trait marker for depression: Evidence from functional neuroimaging

Background:Research using fMRI indicates that sustained limbic activity is linked to processing negative words and self-reported rumination in currently depressed individuals. It is unknown whether this is also present in remitted depressed individuals. We tested the hypothesis that a tendency to ruminate constitutes a trait for depression by using a standard covert fMRI emotional task face in previously and never depressed volunteers and postulated that high rumination scores would correlate with activity in brain areas previously associated with depression.Methods:37 controls (25 female) and 30 remitted depressed (RD, 22 female) were enrolled. Volunteers completed the Ruminative Responses Scale (RRS) and underwent fMRI scanning using a standard covert fMRI emotional task faces. Significance level was set at p < 0.05 (FWE).Results:With RRS score controlled for RD showed reduced subcortical and limbic activity to sad and fearful faces compared to controls. Correlations between RRS scores and neural activity in all participants and control participants alone were very limited. However, in RD, RRS score was negatively correlated with neural response to happy faces and positively correlated with neural response to sad and fearful faces, in cortical and limbic regions associated with depression (hippocampus, thalamus, caudate, insula and cingulate gyrus).Conclusion:The results suggest that reduced limbic activity is associated with remission, possibly as a maintenance mechanism. However, within the remitted group the more ruminative participants show greater response in these areas to negative stimuli, and less to positive stimuli. This could be a neurobiological marker for risk of relapse.

PW07-02 Self-reported rumination as trait marker for depression: Evidence from functional neuroimaging

Background:Research using fMRI indicates that sustained limbic activity is linked to processing negative words and self-reported rumination in currently depressed individuals. It is unknown whether this is also present in remitted depressed individuals. We tested the hypothesis that a tendency to ruminate constitutes a trait for depression by using a standard covert fMRI emotional task face in previously and never depressed volunteers and postulated that high rumination scores would correlate with activity in brain areas previously associated with depression.Methods:37 controls (25 female) and 30 remitted depressed (RD, 22 female) were enrolled. Volunteers completed the Ruminative Responses Scale (RRS) and underwent fMRI scanning using a standard covert fMRI emotional task faces. Significance level was set at p < 0.05 (FWE).Results:With RRS score controlled for RD showed reduced subcortical and limbic activity to sad and fearful faces compared to controls. Correlations between RRS scores and neural activity in all participants and control participants alone were very limited. However, in RD, RRS score was negatively correlated with neural response to happy faces and positively correlated with neural response to sad and fearful faces, in cortical and limbic regions associated with depression (hippocampus, thalamus, caudate, insula and cingulate gyrus).Conclusion:The results suggest that reduced limbic activity is associated with remission, possibly as a maintenance mechanism. However, within the remitted group the more ruminative participants show greater response in these areas to negative stimuli, and less to positive stimuli. This could be a neurobiological marker for risk of relapse

Sleep position alters arousal processes maximally at the high‐risk age for sudden infant death syndrome

An impaired ability to arouse from sleep may play an important role in the pathogenesis of sudden infant death syndrome (SIDS). This study aimed to investigate the effects of prone sleeping on the nature of both induced and spontaneous arousal responses in infants. Thirteen healthy term infants were studied longitudinally at 2-4 weeks, 2-3 months and 5-6 months postnatal age. A pulsatile jet of air to the nostrils was used to induce arousal from both active sleep and quiet sleep in both prone and supine positions. For each stimulus, arousals were classified as sub-cortical activations and cortical arousals, scored using physiological and electroencephalogram changes and expressed as a percentage of the total number of arousals. Spontaneous arousals were similarly analysed. Increased proportions of cortical arousals, hence decreased proportions of sub-cortical activations, were observed in the prone position at 2-3 months. This distinct peak in the proportion of cortical arousals occurred regardless of sleep state and regardless of whether the arousal occurred spontaneously or was induced by air-jet stimulation. The nature of arousal responses in healthy term infants is altered in the prone sleeping position at 2-3 months after birth, the age where SIDS incidence is highest. We postulate that a greater propensity for cortical arousal may be a protective mechanism to promote complete arousal in a vulnerable sleeping position and/or a vulnerable period of maturation. Inadequate or incomplete cortical arousals may explain the increased risk of SIDS associated with the prone position at this age.

Abnormal regional brain function in Parkinson's disease: truth or fiction?

Normalization of regional measurements by the global mean is commonly employed to minimize inter-subject variability in functional imaging studies. This practice is based on the assumption that global values do not substantially differ between patient and control groups. In this issue of NeuroImage, Borghammer and colleagues challenge the validity of this assumption. They focus on Parkinson’s disease (PD) and use computer simulations to show that lower global values can produce spurious increases in subcortical brain regions. The authors speculate that the increased signal observed in these areas in PD is artefactual and unrelated to localized changes in brain function. In this commentary, we summarize what is currently known of the relationship between regional and global metabolic activity in PD and experimental parkinsonism. We found that early stage PD patients exhibit global values that are virtually identical to those of age-matched healthy subjects. SPM analysis revealed increased normalized metabolic activity in a discrete set of biologically relevant subcortical brain regions. Because of their higher variability, the corresponding absolute regional measures did not differ across the two groups. Longitudinal imaging studies in this population showed that the subcortical elevations in normalized metabolism appeared earlier and progressed faster than did focal cortical or global metabolic reductions. The observed increases in subcortical activity, but not the global changes, correlated with independent clinical measures of disease progression. Multivariate analysis with SSM/PCA further confirmed that the abnormal spatial covariance structure of early PD is dominated by these subcortical increases as opposed to network-related reductions in cortical metabolic activity or global changes. Thus, increased subcortical activity in PD cannot be regarded as a simple artefact of global normalization. Moreover, stability of the normalized measurements, particularly at the network level, makes these metabolic indices suitable as imaging biomarkers of PD progression and the treatment response.

FMRI analysis of active, passive and electrically stimulated ankle dorsiflexion

Ankle dorsiflexion (ADF) is an integral component in gait. The objective of this study was to define, using functional magnetic resonance imaging (fMRI) in healthy volunteers ( n = 12), the brain regions that are activated during Electrical Stimulation (ES)-induced ADF movements, and compare this to the pattern of activation occurring during active and passive ADF. Concurrent electromyography (EMG) was used to monitor the tibialis anterior muscle activity so as to allow EMG-guided fMRI analysis to be performed. Patterns of cortical and sub-cortical activation in response to active, passive and ES-induced ADF movement were identified. EMG-guided fMRI analysis was shown to improve detection and reduce inter-session variance for active and ES tasks. A significantly greater number of voxels were activated during active and ES-induced ADF compared to passive ADF in contralateral primary motor (M1), primary sensory (SI), and secondary somatosensory (SII) areas, as well as in supplementary motor area (SMA) and cingulate motor areas (CMA); bilateral dorsal and ventral premotor areas and cerebellum VI. The contrast of active greater than ES-induced ADF showed increased activation in SMA, contralateral PMdr; bilateral PMvr, dorsolateral prefrontal cortex and CMA; and ipsilateral cerebellum IV. Active ADF generated greater activation in brain areas responsible for motor planning, execution and visuomotor co-ordination. ES-induced activation was greater in bilateral SII and insula than for active ADF, hypothesised to result from increased sensory integration, but also possibly due to a nociceptive component to ES.

Changes in cortical and subcortical motor activity in early ALS studied with fMRI

Changes in cortical and subcortical motor activity in early ALS studied with fMRI

Cortical and subcortical contributions to the attentive processing of speech

The neuroanatomical correlates of attentive listening were investigated with functional magnetic resonance imaging and an attention task in which listeners responded only to words that combined two specific attributes of voice and semantic content. This task was performed under two different attentive listening conditions: (i) diotically, with words presented sequentially, and (ii) dichotically, with male and female voices presented simultaneously but segregated to different ears. For both conditions, functional magnetic resonance imaging revealed bihemispheric but right-lateralized activity patterns in mid-prefrontal, anterior cingulate, and inferior parietal areas, as well as significant anterior insular and subcortical activation. Manipulating attentional demands under different listening conditions revealed an important role for right anterior insula, striatum, and thalamus in the regulation of attentive listening to spoken language.

Error-specific medial cortical and subcortical activity during the stop signal task: A functional magnetic resonance imaging study

The ability to detect errors and adjust behavior accordingly is essential for maneuvering in an uncertain environment. Errors are particularly prone to occur when multiple, conflicting responses are registered in a situation that requires flexible behavioral outputs. Previous studies have provided evidence indicating the importance of the medial cortical brain regions including the cingulate cortex in processing conflicting information. However, conflicting situations can be successfully resolved, or lead to errors, prompting a behavioral change in the observers. In particular, how does the brain use error signals specifically to adjust behavior on the fly? Here we employ a stop signal task (SST) to elicit errors approximately half of the time in high-conflict trials despite constant behavioral adjustment of the observers. Using functional magnetic resonance imaging, we show greater and, sequentially, less activation in the medial cortical regions when observers made an error, compared with when they successfully resolved high-conflict responses. Errors also evoked greater activity in the cuneus, retrosplenial cortex, insula, and subcortical structures including the thalamus and the region of the epithalamus (the habenula). We further showed that the error-related medial cortical activities are not correlated with post-error behavioral adjustment, as indexed by post-error slowing (PES) in go trial reaction time. These results delineate an error-specific pattern of brain activation during the SST. The results also suggest that the relationship between error-related activity and post-error behavioral adjustment may be more complicated than has been conceptualized by the conflict monitoring hypothesis.