Comparison of motion correction techniques applied to functional near-infrared spectroscopy data from children (Erratum).

The erratum concerns amendment of Section 2.5 of the published article.

Comparison of motion correction techniques applied to functional near-infrared spectroscopy data from children.

Motion artifacts are the most significant sources of noise in the context of pediatric brain imaging designs and data analyses, especially in applications of functional near-infrared spectroscopy (fNIRS), in which it can completely affect the quality of the data acquired. Different methods have been developed to correct motion artifacts in fNIRS data, but the relative effectiveness of these methods for data from child and infant subjects (which is often found to be significantly noisier than adult data) remains largely unexplored. The issue is further complicated by the heterogeneity of fNIRS data artifacts. We compared the efficacy of the six most prevalent motion artifact correction techniques with fNIRS data acquired from children participating in a language acquisition task, including wavelet, spline interpolation, principal component analysis, moving average (MA), correlation-based signal improvement, and combination of wavelet and MA. The evaluation of five predefined metrics suggests that the MA and wavelet methods yield the best outcomes. These findings elucidate the varied nature of fNIRS data artifacts and the efficacy of artifact correction methods with pediatric populations, as well as help inform both the theory and practice of optical brain imaging analysis.

Words in the bilingual brain: an fNIRS brain imaging investigation of lexical processing in sign-speech bimodal bilinguals.

Early bilingual exposure, especially exposure to two languages in different modalities such as speech and sign, can profoundly affect an individual's language, culture, and cognition. Here we explore the hypothesis that bimodal dual language exposure can also affect the brain's organization for language. These changes occur across brain regions universally important for language and parietal regions especially critical for sign language (Newman et al., 2002). We investigated three groups of participants (N = 29) that completed a word repetition task in American Sign Language (ASL) during fNIRS brain imaging. Those groups were (1) hearing ASL-English bimodal bilinguals (n = 5), (2) deaf ASL signers (n = 7), and (3) English monolinguals naïve to sign language (n = 17). The key finding of the present study is that bimodal bilinguals showed reduced activation in left parietal regions relative to deaf ASL signers when asked to use only ASL. In contrast, this group of bimodal signers showed greater activation in left temporo-parietal regions relative to English monolinguals when asked to switch between their two languages (Kovelman et al., 2009). Converging evidence now suggest that bimodal bilingual experience changes the brain bases of language, including the left temporo-parietal regions known to be critical for sign language processing (Emmorey et al., 2007). The results provide insight into the resilience and constraints of neural plasticity for language and bilingualism.

At the rhythm of language: brain bases of language-related frequency perception in children.

What neural mechanisms underlie language and reading acquisition? Slow rhythmic modulations in the linguistic stream (below 8 Hz) mark syllable and word boundaries in the continuous linguistic stream, potentially helping children master the words and structures of their language. Converging evidence across language and reading research suggests that children's sensitivity to these slow rhythmic modulations is important for language and reading acquisition. In infancy, children produce rhythmically alternating syllables, or babbles, at a slow frequency of ~1.5 Hz or 660 ms (Petitto et al., 2001). In early grades, children's sensitivity to slow rhythmic modulations correlates with their reading ability (Goswami, 2011). We used functional Near Infrared (fNIRS) imaging to investigate the brain bases of "language rhythm" in beginning readers (ages 6-9). Right hemisphere showed an overall greater activation toward the slow rhythmic stimuli, and left hemisphere showed greater activation toward 1.5 Hz, relative to faster and slower frequencies. The findings suggest that while right hemisphere might have an overall better ability to process rhythmic sensitivity, left hemisphere might have a select sensitivity to a preferred range of slow rhythmic modulations-a range that might be particularly salient to brain mechanisms responsible for cross-modal language processing and reading acquisition.

Exploring Cognitive Functions in Babies, Children & Adults with Near Infrared Spectroscopy.

An explosion of functional Near Infrared Spectroscopy (fNIRS) studies investigating cortical activation in relation to higher cognitive processes, such as language, memory, and attention is underway worldwide involving adults, children and infants with typical and atypical cognition. The contemporary challenge of using fNIRS for cognitive neuroscience is to achieve systematic analyses of data such that they are universally interpretable, and thus may advance important scientific questions about the functional organization and neural systems underlying human higher cognition. Existing neuroimaging technologies have either less robust temporal or spatial resolution. Event Related Potentials and Magneto Encephalography (ERP and MEG) have excellent temporal resolution, whereas Positron Emission Tomography and functional Magnetic Resonance Imaging (PET and fMRI) have better spatial resolution. Using non-ionizing wavelengths of light in the near-infrared range (700-1000 nm), where oxy-hemoglobin is preferentially absorbed by 680 nm and deoxy-hemoglobin is preferentially absorbed by 830 nm (e.g., indeed, the very wavelengths hardwired into the fNIRS Hitachi ETG-400 system illustrated here), fNIRS is well suited for studies of higher cognition because it has both good temporal resolution (approximately 5s) without the use of radiation and good spatial resolution (approximately 4 cm depth), and does not require participants to be in an enclosed structure. Participants cortical activity can be assessed while comfortably seated in an ordinary chair (adults, children) or even seated in mom s lap (infants). Notably, NIRS is uniquely portable (the size of a desktop computer), virtually silent, and can tolerate a participants subtle movement. This is particularly outstanding for the neural study of human language, which necessarily has as one of its key components the movement of the mouth in speech production or the hands in sign language. The way in which the hemodynamic response is localized is by an array of laser emitters and detectors. Emitters emit a known intensity of non-ionizing light while detectors detect the amount reflected back from the cortical surface. The closer together the optodes, the greater the spatial resolution, whereas the further apart the optodes, the greater depth of penetration. For the fNIRS Hitachi ETG-4000 system optimal penetration / resolution the optode array is set to 2cm. Our goal is to demonstrate our method of acquiring and analyzing fNIRS data to help standardize the field and enable different fNIRS labs worldwide to have a common background.

Dual language use in sign-speech bimodal bilinguals: fNIRS brain-imaging evidence.

UNLABELLED: The brain basis of bilinguals' ability to use two languages at the same time has been a hotly debated topic. On the one hand, behavioral research has suggested that bilingual dual language use involves complex and highly principled linguistic processes. On the other hand, brain-imaging research has revealed that bilingual language switching involves neural activations in brain areas dedicated to general executive functions not specific to language processing, such as general task maintenance. Here we address the involvement of language-specific versus cognitive-general brain mechanisms for bilingual language processing. We study a unique population, bimodal bilinguals proficient in signed and spoken languages, and we use an innovative brain-imaging technology, functional Near-Infrared Spectroscopy (fNIRS; Hitachi ETG-4000). Like fMRI, the fNIRS technology measures hemodynamic change, but it is also advanced in permitting movement for unconstrained speech and sign production. Participant groups included (i) hearing ASL-English bilinguals, (ii) ASL monolinguals, and (iii) English monolinguals. Imaging tasks included picture naming in "Monolingual mode" (using one language at a time) and in "Bilingual mode" (using both languages either simultaneously or in rapid alternation). Behavioral results revealed that accuracy was similar among groups and conditions. By contrast, neuroimaging results revealed that bilinguals in Bilingual mode showed greater signal intensity within posterior temporal regions ("Wernicke's area") than in Monolingual mode. SIGNIFICANCE: Bilinguals' ability to use two languages effortlessly and without confusion involves the use of language-specific posterior temporal brain regions. This research with both fNIRS and bimodal bilinguals sheds new light on the extent and variability of brain tissue that underlies language processing, and addresses the tantalizing questions of how language modality, sign and speech, impact language representation in the 7 brain.

Shining new light on the brain's "bilingual signature": a functional Near Infrared Spectroscopy investigation of semantic processing.

Decades of research have shown that, from an early age, proficient bilinguals can speak each of their two languages separately (similar to monolinguals) or rapidly switch between them (dissimilar to monolinguals). Thus we ask, do monolingual and bilingual brains process language similarly or dissimilarly, and is this affected by the language context? Using an innovative brain imaging technology, functional Near Infrared Spectroscopy (fNIRS), we investigated how adult bilinguals process semantic information, both in speech and in print, in a monolingual language context (one language at a time) or in a bilingual language context (two languages in rapid alternation). While undergoing fNIRS recording, ten early exposed, highly proficient Spanish-English bilinguals completed a Semantic Judgment task in monolingual and bilingual contexts and were compared to ten English monolingual controls. Two hypotheses were tested: the Signature Hypothesis predicts that early, highly proficient bilinguals will recruit neural tissue to process language differently from monolinguals across all language contexts. The Switching Hypothesis predicts that bilinguals will recruit neural tissue to process language similarly to monolinguals, when using one language at a time. Supporting the Signature Hypothesis, in the monolingual context, bilinguals and monolinguals showed differences in both hemispheres in the recruitment of DLPFC (BA 46/9) and IFC (BA 47/11), but similar recruitment of Broca's area (BA 44/45). In particular, in the monolingual context, bilinguals showed greater signal intensity in channels maximally overlaying DLPFC and IFC regions as compared to monolinguals. In the bilingual context, bilinguals demonstrated a more robust recruitment of right DLPFC and right IFC. These findings reveal how extensive early bilingual exposure modifies language organization in the brain-thus imparting a possible "bilingual signature." They further shed fascinating new light on how the bilingual brain may reveal the biological extent of the neural architecture underlying all human language and the language processing potential not fully recruited in the monolingual brain.

Stimulus-induced changes in blood flow and 2-deoxyglucose uptake dissociate in ipsilateral somatosensory cortex.

The present study addresses the relationship between blood flow and glucose consumption in rat primary somatosensory cortex (SI) in vivo. We examined bilateral neuronal and hemodynamic changes and 2-deoxyglucose (2DG) uptake, as measured by autoradiography, in response to unilateral forepaw stimulation. In contrast to the contralateral forepaw area, where neuronal activity, blood oxygenation/flow and 2DG uptake increased in unison, we observed, in the ipsilateral SI, a blood oxygenation/flow decrease and arteriolar vasoconstriction in the presence of increased 2DG uptake. Laminar electrophysiological recordings revealed an increase in ipsilateral spiking consistent with the observed increase in 2DG uptake. The vasoconstriction and the decrease in blood flow in the presence of an increase in 2DG uptake in the ipsilateral SI contradict the prominent metabolic hypothesis regarding the regulation of cerebral blood flow, which postulates that the state of neuroglial energy consumption determines the regional blood flow through the production of vasoactive metabolites. We propose that other factors, such as neuronal (and glial) release of messenger molecules, might play a dominant role in the regulation of blood flow in vivo in response to a physiological stimulus.

Effects of serotonin on the intrinsic membrane properties of layer II medial entorhinal cortex neurons.

Although serotonin (5-HT) is an important neuromodulator in the superficial layers of the medial entorhinal cortex (mEC), there is some disagreement concerning its influences upon the membrane properties of neurons within this region. We performed whole cell recordings of mEC Layer II projection neurons in rat brain slices in order to characterize the intrinsic influences of 5-HT. In current clamp, 5-HT evoked a biphasic response consisting of a moderately short latency and large amplitude hyperpolarization followed by a slowly developing, long lasting, and small amplitude depolarization. Correspondingly, in voltage clamp, 5-HT evoked a robust outward followed by a smaller inward shift of holding current. The outward current evoked by 5-HT showed a consistent current/voltage (I/V) relationship across cells with inward rectification, and demonstrating a reversal potential that was systematically dependent upon the extracellular concentration of K(+), suggesting that it was predominantly carried by potassium ions. However, the inward current showed a less consistent I/V relationship across different cells, suggesting multiple independent ionic mechanisms. The outward current was mediated through activation of 5-HT(1A) receptors via a G-protein dependent mechanism while inward currents were evoked in a 5-HT(1A)-independent fashion. A significant proportion of the inward current was blocked by the I(h) inhibitor ZD7288 and appeared to be due to 5-HT modulation of I(h) as 5-HT shifted the activation curve of I(h) in a depolarizing fashion. Serotonin is thus likely to influence, in a composite fashion, the information processing of Layer II neurons in the mEC and thus, the passage of neocortical information via the perforant pathway to the hippocampus.

Abolition of spindle oscillations and 3-Hz absence seizurelike activity in the thalamus by using high-frequency stimulation: potential mechanism of action.

OBJECT: The mechanism of action whereby high-frequency stimulation (HFS) in the thalamus ameliorates tremor and epilepsy is unknown. The authors studied the effects of HFS on thalamocortical relay neurons in a ferret in vitro slice preparation to test the hypothesis that HFS abolishes synchronized oscillations by neurotransmitter release. METHODS: Intracellular and extracellular electrophysiological recordings were made in thalamic slices. The neurons in the thalamic slice spontaneously generated spindle oscillations, and treatment with picrotoxin, a gamma-aminobutyric acid A receptor antagonist, resulted in 3- to 4-Hz absence seizurelike activity. High-frequency stimulation (stimulation parameters: 10-1000-microA amplitude; l00-microsec pulse width; 100-Hz frequency; 1-60 seconds) was applied using a concentric bipolar stimulating electrode placed adjacent to the recording electrodes. High-frequency stimulation within the thalamus generated inhibitory and excitatory postsynaptic potentials, membrane depolarization, an increase in action potential firing during the stimulation period, and abolished the spindle oscillations in the thalamocortical relay neurons. High-frequency stimulation applied to 20-microM picrotoxin-treated slices eliminated the 3- to 4-Hz absence seizurelike activity. CONCLUSIONS: High-frequency stimulation eliminates spontaneous spindle oscillations and picrotoxin-induced absence seizurelike activity in thalamic slices by synaptic neurotransmitter release; thus, HFS may abolish synchronous oscillatory activities such as those that generate tremor and seizures. Paradoxically, HFS, which is excitatory, and surgical lesions of the ventrointermedius thalamus, which are presumably inhibitory, both suppress tremors. This paradox is resolved by recognizing that HFS-mediated neurotransmitter release and thalamic surgery both disrupt the circuit generating tremor or seizure, albeit by different mechanisms.

Spike patterning by Ca2+-dependent regulation of a muscarinic cation current in entorhinal cortex layer II neurons.

In entorhinal cortex layer II neurons, muscarinic receptor activation promotes depolarization via activation of a nonspecific cation current (I(NCM)). Under muscarinic influence, these neurons also develop changes in excitability that result in activity-dependent induction of delayed firing and bursting activity. To identify the membrane processes underlying these phenomena, we examined whether I(NCM) may undergo activity-dependent regulation. Our voltage-clamp experiments revealed that appropriate depolarizing protocols increased the basal level of inward current activated during muscarinic stimulation and suggested that this effect was due to I(NCM) upregulation. In the presence of low buffering for intracellular Ca(2+), this upregulation was transient, and its decay could be followed by a phase of I(NCM) downregulation. Both up- and downregulation were elicited by depolarizing stimuli able to activate voltage-gated Ca(2+) channels (VGCC); both were sensitive to increasing concentrations of intracellular Ca(2+)-chelating agents with downregulation being abolished at lower Ca(2+)-buffering capacities; both were reduced or suppressed by VGCC block or in the absence of extracellular Ca(2+). These data indicate that relatively small increases in [Ca(2+)](i) driven by firing activity can induce upregulation of a basal muscarinic depolarizing-current level, whereas more pronounced [Ca(2+)](i) elevations can result in I(NCM) downregulation. We propose that the interaction of activity-dependent positive and negative feedback mechanisms on I(NCM) allows entorhinal cortex layer II neurons to exhibit emergent properties, such as delayed firing and enhanced or suppressed responses to repeated stimuli, that may be of importance in the memory functions of the temporal lobe and in the pathophysiology of epilepsy.

Muscarinic activation of a cation current and associated current noise in entorhinal-cortex layer-II neurons.

The effects of muscarinic stimulation on the membrane potential and current of in situ rat entorhinal-cortex layer-II principal neurons were analyzed using the whole cell, patch-clamp technique. In current-clamp experiments, application of carbachol (CCh) induced a slowly developing, prolonged depolarization initially accompanied by a slight decrease or no significant change in input resistance. By contrast, in a later phase of the depolarization input resistance appeared consistently increased. To elucidate the ionic bases of these effects, voltage-clamp experiments were then carried out. In recordings performed in nearly physiological ionic conditions at the holding potential of -60 mV, CCh application promoted the slow development of an inward current deflection consistently associated with a prominent increase in current noise. Similarly to voltage responses to CCh, this inward-current induction was abolished by the muscarinic antagonist, atropine. Current-voltage relationships derived by applying ramp voltage protocols during the different phases of the CCh-induced inward-current deflection revealed the early induction of an inward current that manifested a linear current/voltage relationship in the subthreshold range and the longer-lasting block of an outward K(+) current. The latter current could be blocked by 1 mM extracellular Ba(2+), which allowed us to study the CCh-induced inward current (I(CCh)) in isolation. The extrapolated reversal potential of the isolated I(CCh) was approximately 0 mV and was not modified by complete substitution of intrapipette K(+) with Cs(+). Moreover, the extrapolated I(CCh) reversal shifted to approximately -20 mV on removal of 50% extracellular Na(+). These results are consistent with I(CCh) being a nonspecific cation current. Finally, noise analysis of I(CCh) returned an estimated conductance of the underlying channels of approximately 13.5 pS. We conclude that the depolarizing effect of muscarinic stimuli on entorhinal-cortex layer-II principal neurons depends on both the block of a K(+) conductance and the activation of a "noisy" nonspecific cation current. We suggest that the membrane current fluctuations brought about by I(CCh) channel noise may facilitate the "theta" oscillatory dynamics of these neurons and enhance firing reliability and synchronization.