Subcortical Activity Research Articles

Short- and long-latency somatosensory neuronal responses reveal selective brain injury and effect of hypothermia in global hypoxic ischemia

Evoked potentials recorded from the somatosensory cortex have been shown to be an electrophysiological marker of brain injury in global hypoxic ischemia (HI). The evoked responses in somatosensory neurons carry information pertaining to signal from the ascending pathway in both the subcortical and cortical areas. In this study, origins of the subcortical and cortical signals are explored by decomposing the evoked neuronal activities into short- and long-latency responses (SLR and LLR), respectively. We evaluated the effect of therapeutic hypothermia on SLR and LLR during early recovery from cardiac arrest (CA)-induced HI in a rodent model. Twelve rats were subjected to CA, after which half of them were treated with hypothermia (32-34°C) and the rest were kept at normal temperature (36-37°C). Evoked neuronal activities from the primary somatosensory cortex, including multiunit activity (MUA) and local field potential (LFP), were continuously recorded during injury and early recovery. Results showed that upon initiation of injury, LLR disappeared first, followed by the disappearance of SLR, and after a period of isoelectric silence SLR reappeared prior to LLR. This suggests that cortical activity, which primarily underlies the LLR, may be more vulnerable to ischemic injury than SLR, which relates to subcortical activity. Hypothermia potentiated the SLR but suppressed the LLR by delaying its recovery after CA (hypothermia: 38.83 ± 5.86 min, normothermia: 23.33 ± 1.15 min; P < 0.05) and attenuating its amplitude, suggesting that hypothermia may selectively downregulate cortical activity as an approach to preserve the cerebral cortex. In summary, our study reveals the vulnerability of the somatosensory neural structures to global HI and the differential effects of hypothermia on these structures.

Imaging the Motor System

Using functional magnetic resonance imaging at 3.0 T, we have focused on motor preparation, defined as the phase in which elemental attributes of subsequent voluntary motor outputs are determined. Previous imaging studies have succeeded in the characterization of premotor and parietal activation patterns during motor preparation, but subcortical activation patterns remained far less well defined. Our studies have provided converging evidence for a specific involvement of the anterior putamen and the adjacent dorsolateral caudate nucleus during motor preparatory phases, in which either temporal or spatial attributes of movements are defined; activity then shifts into more posterior parts of the putamen during motor execution phases. Hence, fMRI allowed for characterization of rostro-caudal activation shifts from motor planning to execution. The described activation patterns represent targets of the associative, and sensori-motor cortical projection sites to the basal ganglia. Currently, applications in disorders of movement are under way, including task-specific dystonia and Parkinson's disease, and it is expected that these imaging studies, by focusing on motor preparation phases, will extend current imaging findings in movement disorders. Indeed, studying motor preparation phases allows to study motor deficits at a conceptual stage of motor processing.

Distinct but overlapping neural networks subserve depression and insecure attachment

Insecure attachment has been linked to depression and to outcome in psychotherapy. The neural mechanisms subserving the relationship between attachment security and depression are not well understood. We have developed a method to examine attachment-related brain activity in depression. Twenty-eight women, half depressed, viewed images of their mother, a female friend, and female strangers during fMRI scanning. The effects of depression and insecure attachment were determined with whole-brain multiple linear regression of blood-oxygen-level-dependent response against subjects' Beck Depression Inventory and Adult Attachment Interview (AAI) coherence of mind scores. Interaction effects were analyzed with ANOVA. Activity associated with depression and with insecure attachment was found in the cortico-striato-thalamic circuits of affect regulation. For early attachment (mother-friend contrast), depression scores correlated with activation of cortical and sub-cortical components of these circuits, while attachment insecurity correlated with sub-cortical activity in the same circuitry. Depression and attachment insecurity correlated with both cortical and sub-cortical activities for mother-stranger, and areas of overlap and of enhancing interactions between depression and insecure attachment were found. For late attachment (friend-stranger contrast), only cortical effects were found. Depression and attachment insecurity may be subserved by similar but distinct components of affect regulating circuits. Their interactions may explain the greater difficulty of treating depression in insecurely attached patients and suggest a contributing role for insecure attachment in depression. Further, differential sub-cortical vs cortical encoding of early vs late attachment suggests a top-down model of late attachment, potentially relevant to psychotherapeutic outcome.

Importance of reward and prefrontal circuitry in hunger and satiety: Prader–Willi syndrome vs simple obesity

BackgroundThe majority of research on obesity has focused primarily on clinical features (eating behavior, adiposity measures), or peripheral appetite-regulatory peptides (leptin, ghrelin). However, recent functional neuroimaging studies have demonstrated that some reward circuitry regions which are associated with appetite-regulatory hormones are also involved in the development and maintenance of obesity. Prader-Willi syndrome (PWS), characterized by hyperphagia and hyperghrelinemia reflecting multi-system dysfunction in inhibitory and satiety mechanisms, serves as an extreme model of genetic obesity. Simple (non-PWS) obesity (OB) represents an obesity control state.ObjectiveThis study investigated subcortical food motivation circuitry and prefrontal inhibitory circuitry functioning in response to food stimuli before and after eating in individuals with PWS compared with OB. We hypothesized that groups would differ in limbic regions (i.e., hypothalamus, amygdala) and prefrontal regions associated with cognitive control [i.e., dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC)] after eating.Design and ParticipantsFourteen individuals with PWS, 14 BMI- and age-matched individuals with OB, and 15 age-matched healthy-weight controls (HWC) viewed food and non-food images while undergoing functional MRI before (pre-meal) and after (post-meal) eating. Using SPM8, group contrasts were tested for hypothesized regions: hypothalamus, nucleus accumbens (NAc), amygdala, hippocampus, OFC, medial PFC, and DLPFC.ResultsCompared with OB and HWC, PWS demonstrated higher activity in reward/limbic regions (NAc, amygdala) and lower activity in hypothalamus and hippocampus, in response to food (vs. non-food) images pre-meal. Post-meal, PWS exhibited higher subcortical activation (hypothalamus, amygdala, hippocampus) compared to OB and HWC. OB showed significantly higher activity versus PWS and HWC in cortical regions (DLPFC, OFC) associated with inhibitory control.ConclusionIn PWS compared with obesity per se, results suggest hyperactivations in subcortical reward circuitry and hypoactivations in cortical inhibitory regions after eating, which provides evidence of neural substrates associated with variable abnormal food motivation phenotypes in PWS and simple obesity.

Remembering forward: Neural correlates of memory and prediction in human motor adaptation

We used functional MR imaging (FMRI), a robotic manipulandum and systems identification techniques to examine neural correlates of predictive compensation for spring-like loads during goal-directed wrist movements in neurologically-intact humans. Although load changed unpredictably from one trial to the next, subjects nevertheless used sensorimotor memories from recent movements to predict and compensate upcoming loads. Prediction enabled subjects to adapt performance so that the task was accomplished with minimum effort. Population analyses of functional images revealed a distributed, bilateral network of cortical and subcortical activity supporting predictive load compensation during visual target capture. Cortical regions--including prefrontal, parietal and hippocampal cortices--exhibited trial-by-trial fluctuations in BOLD signal consistent with the storage and recall of sensorimotor memories or "states" important for spatial working memory. Bilateral activations in associative regions of the striatum demonstrated temporal correlation with the magnitude of kinematic performance error (a signal that could drive reward-optimizing reinforcement learning and the prospective scaling of previously learned motor programs). BOLD signal correlations with load prediction were observed in the cerebellar cortex and red nuclei (consistent with the idea that these structures generate adaptive fusimotor signals facilitating cancelation of expected proprioceptive feedback, as required for conditional feedback adjustments to ongoing motor commands and feedback error learning). Analysis of single subject images revealed that predictive activity was at least as likely to be observed in more than one of these neural systems as in just one. We conclude therefore that motor adaptation is mediated by predictive compensations supported by multiple, distributed, cortical and subcortical structures.

Fewer Spontaneous Arousals in Infants with Apparent Life-Threatening Event

A deficit in arousal process has been implicated as a mechanism of sudden infant death syndrome (SIDS). Compared with control infants, SIDS victims showed significantly more subcortical activations and fewer cortical arousals than matched control infants. Apparent life-threatening event (ALTE) is often considered as an aborted SIDS event. The aim of this study was to study the arousal characteristics of ALTE infants during the first months of life. 35 ALTE infants were studied with nighttime polysomnography at 2-3, 5-6, and 8-9 months of age. Eighteen of the infants had mothers who smoked. The infants were born full term and were usually supine sleepers. Sleep state and cardiorespiratory parameters were scored according to recommended criteria. Arousals were differentiated into subcortical activations or cortical arousals, according to the presence of autonomic and/or electroencephalographic changes. The results were compared with those of 19 healthy infants with nonsmoking mothers. During NREM sleep, the ALTE infants had fewer total arousals, cortical arousals, and subcortical activations at 2-3 and 5-6 months (P < 0.001) than control infants. ALTE infants with smoking mothers had more obstructive apnea (P = 0.009) and more subcortical activations during REM sleep at 2-3 months of age (P < 0.001) than ALTE infants with nonsmoking mothers. Spontaneous arousals were differently altered in ALTE infants than in SIDS infants, suggesting an entity different from SIDS. ALTE infants with smoking mothers had arousal and respiratory characteristics that were similar to future SIDS victims, suggesting some common abnormalities in brainstem dysfunction.

EEG spectral analysis of apnoeic events confirms visual scoring in childhood sleep disordered breathing

This study compared electroencephalogram (EEG) spectral analysis with standard visual scoring to assess the validity of clinical classification of arousals at respiratory event termination in children with obstructive sleep apnoea (OSA). Twenty children (six M/14F) aged 7-12years, diagnosed with moderate to severe OSA participated in this study. Overnight polysomnography was performed, and sleep stages and arousals visually scored using clinical paediatric measures. The EEG was spectrally analysed in six 5-s epochs across respiratory events, namely two consecutive 5-s epochs pre-event onset and a 5s epoch post-event onset, 5-s before event termination, and two contiguous 5-s epochs post-event termination. EEG spectral power distribution was compared across respiratory events visually categorised as full cortical arousals, subcortical activations, or non-arousals using specialised software (Sleep Research System 5.0). There was no difference in power spectra between events in REM and NREM sleep and these were combined. There was a statistically significant fall from pre-arousal baseline values in delta and theta spectral power at respiratory event terminations associated with cortical arousals only. No change in power was detected at respiratory event terminations associated with subcortical activations or non-arousals. The lack of significant EEG spectral power changes at respiratory event terminations not associated with visually identified cortical arousals indicates undetected micro-arousals are not present. The results support the validity of clinical classifications of arousals at respiratory event termination.

Segregation of frontoparietal and cerebellar components within saccade and vergence networks using hierarchical independent component analysis of fMRI

Cortical and subcortical functional activity stimulated via saccade and vergence eye movements were investigated to examine the similarities and differences between networks and regions of interest (ROIs). Blood oxygenation level-dependent (BOLD) signals from stimulus-induced functional Magnetic Resonance Imaging (MRI) experiments were analyzed studying 16 healthy subjects. Six types of oculomotor experiments were conducted using a block design to study both saccade and vergence circuits. The experiments included a simple eye movement task and a more cognitively demanding prediction task. A hierarchical independent component analysis (ICA) process began by analyzing individual subject data sets with spatial ICA to extract spatial independent components (sIC), which resulted in three ROIs. Using the time series from each of the three ROIs per subject, per oculomotor experiment, a temporal ICA was used to compute individual temporal independent components (tICs). For each of the three ROIs, the individual tICs from multiple subjects were entered into a second temporal ICA to compute group-level tICs for comparison. Two independent spatial maps were observed for each subject (one sIC showing activity in the frontoparietal regions and another sIC in the cerebellum) during the six oculomotor tasks. Analysis of group-level tICs revealed an increased latency in the cerebellar region when compared to the frontoparietal region. Shared neuronal behavior has been reported in the frontal and parietal lobes, which may in part explain the segregation of frontoparietal functional activity into one sIC. The cerebellum uses multiple time scales for motor learning. This may result in an increased latency observed in the BOLD signal of the cerebellar group-level tIC when compared to the frontal and parietal group-level tICs. The increased latency offers a possible explanation to why ICA dissects the cerebellar activity into an sIC. The hierarchical ICA process used to calculate group-level tICs can yield insight into functional connectivity within complex neural networks.

The effect of serotonergic lesions in the medial prefrontal cortex on psychotomimetic drug-induced locomotor hyperactivity and prepulse inhibition in rats

While dysfunction of the prefrontal cortex has been repeatedly implicated in the pathophysiology of schizophrenia, the role of serotonin in this brain region in schizophrenia is unclear. We therefore examined the effects of local serotonin depletion in the medial prefrontal cortex on psychotomimetic drug-induced locomotor hyperactivity and prepulse inhibition, two animal models of aspects of schizophrenia. Pentobarbital-anaesthetised (60 mg/kg, i.p.) male Sprague-Dawley rats were stereotaxically micro-injected with 0.5 μl of a 5 μg/μl solution of the serotonin neurotoxin 5,7-dihydroxytryptamine into the medial prefrontal cortex. Two weeks after the surgery, rats underwent behavioural testing. When compared to sham-operated controls, rats with me dial prefrontal cortical lesions did not show changes in either psychotomimetic drug-induced locomotor hyperactivity or prepulse inhibition. However, following the administration of the serotonin neurotoxin into the medial prefrontal cortex, the concentration of serotonin was reduced by 60%. These results suggest that serotonin depletion in the medial prefrontal cortex does not lead to dysregulation of subcortical dopaminergic activity and does not cause aberrant responses to environmental stimuli.

Electroencephalographic and Behavioral Studies of Monomethyl Hydrazine Toxicity in the Cat

ABSTRACT The toxicity of monomethyl hydrazine (MMH) administered intraperitoneally in the cat was studied by reference to behavioral and neurophysiological indices. The acute lethal toxicity value (LD50) for MMH was established at 15 mg/kg, and the convulsive toxicity value (CD50) at 7 m/kg. Doses of 18, 9, and 5 mg/kg were then studied systematically in an effort to classify lethal, convulsive, and subconvulsive symptoms. For these doses, a preconvulsive syndrome was described involving recurrent and sustained symptoms, including vomiting, panting, rapid respiration, viscous salivation, hyperactivity, and subcortical seizure activity. The onset latency of these symptoms was directly related to dose. Several lines of evidence suggested at least a partial independence between biochemical and neurophysiological events responsible, on one hand, for convulsions and, on the other, for this preconvulsive syndrome. Convulsions were specifically delayed or prevented in animals trained to suppress movement through...

Evidence for Cortical Automaticity in Rule-Based Categorization

There is evidence that rule-based category learning is supported by a broad neural network that includes the prefrontal cortex, the anterior cingulate cortex, the head of the caudate nucleus, and medial temporal lobe structures. Although thousands of studies have examined rule-based category learning, only a few have studied the development of automaticity in rule-based tasks. Categorizing by a newly learned rule makes heavy demands on declarative memory, but after thousands of repetitions rule-based categorizations are made with no apparent effort. Thus, it seems likely that the neural systems that mediate automatic rule-based categorization are substantially different from the systems that mediate initial learning. This research aims at identifying the neural systems responsible for early and late rule-based categorization performances. Toward this end, this article reports the results of an experiment in which human participants each practiced a rule-based categorization task for >10,000 trials distributed over 20 separate sessions. Sessions 1, 4, 10, and 20 were performed inside a magnetic resonance imaging scanner. The main findings are as follows: (1) cortical activation remained approximately constant throughout training, (2) subcortical activation increased with practice (i.e., there were more activated voxels in the striatum), and (3) only cortical activation was correlated with accuracy after extensive training. The results suggest an initial subcortical neural system centered around the head of the caudate that is gradually replaced by a cortical system centered around the ventrolateral prefrontal cortex. With extensive practice, the cortical system progressively becomes more caudal and dorsal, and is eventually centered around the premotor cortex.

Neural bases of the non-conscious perception of emotional signals

Many emotional stimuli are processed without being consciously perceived. Recent evidence indicates that subcortical structures have a substantial role in this processing. These structures are part of a phylogenetically ancient pathway that has specific functional properties and that interacts with cortical processes. There is now increasing evidence that non-consciously perceived emotional stimuli induce distinct neurophysiological changes and influence behaviour towards the consciously perceived world. Understanding the neural bases of the non-conscious perception of emotional signals will clarify the phylogenetic continuity of emotion systems across species and the integration of cortical and subcortical activity in the human brain.

Sleeping like a baby--does gender influence infant arousability?

Victims of the sudden infant death syndrome (SIDS) may have preexisting abnormalities in their arousal pathways, inhibiting the progression of subcortical activation (SCA) to full cortical arousal (CA). Approximately 60% of SIDS victims are male, and it has been suggested that male infants have delayed cortical maturation compared to females. We hypothesized that CA frequency would be lower and CA threshold would be higher in male infants during both active (AS) and quiet (QS) sleep. 50 healthy term infants (21 male, 29 female) were studied with daytime polysomnography at 2-4 weeks and 2-3 months after birth. Arousal from sleep was induced using a pulsatile air-jet to the nostrils at increasing pressures. At 2-4 weeks, arousability from AS was similar in males and females, however during QS, male infants required a lower stimulus to induce SCA and CA. This gender difference in arousal threshold was not observed at 2-3 months. CA frequencies were similar between genders during both sleep states at both ages, though overall, CA was more frequent in AS than in QS. This study demonstrated that at 2-4 weeks, male infants were easier to arouse than female infants during QS. There were no significant effects of gender on total arousability or SCA and CA frequencies at 2-3 months, the age of peak SIDS incidence. Thus, although male infants are at greater risk of SIDS than female infants, this difference is unlikely to be associated with gender differences in CA threshold or frequency.

A cerebellar thalamic cortical circuit for error-related cognitive control

Error detection and behavioral adjustment are core components of cognitive control. Numerous studies have focused on the anterior cingulate cortex (ACC) as a critical locus of this executive function. Our previous work showed greater activation in the dorsal ACC and subcortical structures during error detection, and activation in the ventrolateral prefrontal cortex (VLPFC) during post-error slowing (PES) in a stop signal task (SST). However, the extent of error-related cortical or subcortical activation across subjects was not correlated with VLPFC activity during PES. So then, what causes VLPFC activation during PES? To address this question, we employed Granger causality mapping (GCM) and identified regions that Granger caused VLPFC activation in 54 adults performing the SST during fMRI. These brain regions, including the supplementary motor area (SMA), cerebellum, a pontine region, and medial thalamus, represent potential targets responding to errors in a way that could influence VLPFC activation. In confirmation of this hypothesis, the error-related activity of these regions correlated with VLPFC activation during PES, with the cerebellum showing the strongest association. The finding that cerebellar activation Granger causes prefrontal activity during behavioral adjustment supports a cerebellar function in cognitive control. Furthermore, multivariate GCA described the “flow of information” across these brain regions. Through connectivity with the thalamus and SMA, the cerebellum mediates error and post-error processing in accord with known anatomical projections. Taken together, these new findings highlight the role of the cerebello-thalamo-cortical pathway in an executive function that has heretofore largely been ascribed to the anterior cingulate-prefrontal cortical circuit.

Electrical source dynamics in three functional localizer paradigms

The visual cortex exhibits functional specialization that can be routinely demonstrated using hemodynamic measures like fMRI and PET. To understand the dynamic nature of cortical processes, however, source imaging with a high temporal resolution is necessary. Here, we asked how well distributed EEG source localization (LAURA) identifies functionally specialized visual processes. We tested three stimulus paradigms commonly used in fMRI with the aim to localize striate cortex, motion-sensitive areas, and face-sensitive areas. EEG source localization showed initial activations in striate and extra-striate areas at around 70ms after stimulus onset. These were quickly followed by extensive cortical, as well as subcortical activation. Functional motion and face-selective areas were localized with margins of below 2cm, at around 170 and 150ms, respectively. The results furthermore show for the first time that the C1 component has generators in the insula and frontal eye fields, but also in subcortical areas like the parahippocampus and the thalamus.

Perceptual organization and visual search processes during target detection task performance in schizophrenia, as revealed by fMRI

BackgroundPast studies of perceptual organization in schizophrenia have demonstrated impairments binding fragmented stimulus components into unified representations. ERP and fMRI data indicate that even under conditions of adequate behavioral task performance, significant and meaningful changes in cortical and subcortical activation are present. Here, we examined, using fMRI, activation differences on a visual task wherein feature grouping was a precursor to the formation of distinct groups in the service of target location and identification. MethodFourteen schizophrenia patients and 16 healthy controls completed a target detection task with 2 conditions: one in which target–distractor grouping facilitates detection (the Isolated condition) and one in which it hinders detection (the Embedded condition). Stimuli were blocked by condition. Accuracy and RT data were obtained in addition to fMRI data. ResultsPatients and controls did not differ significantly in accuracy or RT in either condition. Within this context, controls demonstrated greater recruitment of brain regions involved in visual–spatial processing, and the groups differed in activity in areas known to support visual search, visual analysis, decision making and response generation. ConclusionThese findings are consistent with past data indicating reduced processing of stimulus organization, and the subsequent use of inefficient visual search strategies, even under conditions when behavioral performance is at a high level and matches that of healthy controls.

Cerebral cortical and subcortical cholinergic deficits in parkinsonian syndromes

Cholinergic projections to cerebral cortical and subcortical regions are decreased in Parkinson disease (PD), but not evaluated in the parkinsonian syndromes of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP). We studied cholinergic innervation in these disorders as compared to age-appropriate normal control subjects. We used PET with [(11)C]PMP to measure acetylcholinesterase (AChE) activity in multiple cerebral cortical and subcortical regions. We studied 22 normal controls, 12 patients with PD, 13 patients with MSA-P, and 4 patients with PSP. We found significantly decreased AChE activity in most cerebral cortical regions in PD and MSA-P, and a similar but nonsignificant decrease in PSP. No differences were found between PD and MSA-P. Significantly decreased AChE activity was found in PD in striatum, cerebellum, and thalamus, with a marginally significant decrease in mesencephalon and no change in pons. Significantly greater declines in AChE activity in all subcortical regions were seen in MSA-P and PSP vs in PD. Decreased AChE activity in brainstem and cerebellum of all 3 disorders correlated with disturbances of balance and gait. Cerebral cortical cholinergic activity is decreased to a similar level in Parkinson disease (PD), parkinsonian syndromes of multiple system atrophy (MSA-P), and progressive supranuclear palsy (PSP) as compared to normal controls. Subcortical cholinergic activity is significantly more decreased in MSA-P and PSP than in PD. The more substantial decrease reflects greater impairment in the pontine cholinergic group, which is important in motor activity, particularly gait. These differences may account for the greater gait disturbances in the early stages of MSA-P and PSP than in PD.

"Splitting of the Mind" Revisited: Recent Neuroimaging Evidence for Functional Dysconnection in Schizophrenia and Its Relation to Symptoms

"Splitting of the Mind" Revisited: Recent Neuroimaging Evidence for Functional Dysconnection in Schizophrenia and Its Relation to Symptoms

Selective Regions of the Visuomotor System Are Related to Gain-Induced Changes in Force Error

When humans perform movements and receive on-line visual feedback about their performance, the spatial qualities of the visual information alter performance. The spatial qualities of visual information can be altered via the manipulation of visual gain and changes in visual gain lead to changes in force error. The current study used functional magnetic resonance imaging during a steady-state precision grip force task to examine how cortical and subcortical brain activity can change with visual gain induced changes in force error. Small increases in visual gain < 1° were associated with a substantial reduction in force error and a small increase in the spatial amplitude of visual feedback. These behavioral effects corresponded with an increase in activation bilaterally in V3 and V5 and in left primary motor cortex and left ventral premotor cortex. Large increases in visual gain > 1° were associated with a small change in force error and a large change in the spatial amplitude of visual feedback. These behavioral effects corresponded with increased activity bilaterally in dorsal and ventral premotor areas and right inferior parietal lobule. Finally, activity in the left and right lobule VI of the cerebellum and left and right putamen did not change with increases in visual gain. Together, these findings demonstrate that the visuomotor system does not respond uniformly to changes in the gain of visual feedback. Instead, specific regions of the visuomotor system selectively change in activity related to large changes in force error and large changes in the spatial amplitude of visual feedback.

Stimulus type does not affect infant arousal response patterns

Previous studies have examined infant arousal responses to various arousal stimuli; however it is unclear whether the patterns of responses to different stimuli are comparable within subjects across early development. The aim of the study was to compare the effects of both respiratory and somatosensory stimulation on arousal processes in the same infants throughout the first 6 months of life. Ten healthy term infants were studied with daytime polysomnography at 2-4 weeks, 2-3 and 5-6 months. Infants were challenged with both hypoxia (15% O(2), balanced N(2)) and a pulsatile air-jet to the nostrils. Stimulus-induced sub-cortical activations (SCA) and cortical arousals (CA) were expressed as percentages of total arousals. Heart rate (HR) changes and electroencephalogram (EEG) desynchronization were also contrasted for the two stimuli. During active sleep (AS), there was no significant effect of stimulus type on proportions of CA at any of the ages studied. During quiet sleep (QS), hypoxia elicited higher CA proportions than the air-jet at 2-3 and 5-6 months (P < 0.01). Overall, HR responses associated with SCA and CA and the duration of EEG desynchronization during CA were similar for both stimuli. Mild hypoxia and nasal air-jet stimulation produce qualitatively similar patterns of arousal responses during the first 6 months of life, supporting the concept of a final common neural pathway of cortical activation. Quantitatively, full CA from QS is more likely with hypoxia, in keeping with it being a life-threatening stimulus. This study supports the nasal air-jet as an appropriate stimulus for assessing developmental patterns of infant arousal process.