Cortical cerebral atrophy in patients with Parkinson’s disease: New opportunities for in vivo diagnostics

The Parkinson’s disease (PD) pathology is not limited to degeneration of the nigrostriatal dopaminergic system, but also includes the wide lesion of various regions of cerebral cortex. In our study we aimed to identify differences in the brain cortical thickness in patients with early and advanced PD using MRI morphometry. Sixty-seven patients with Hoehn–Yahr stages 2 and 3 were examined. All patients underwent MRI with subsequent post-processing and estimation of cortical thickness values in different brain regions. Significant differences in the visual and cingulate cortex, fusiform gyri, frontopolar zone of a dominant hemisphere, and Brodmann’s areas 1, 2, 3, and 4 of a non-dominant hemisphere were obtained. These data show relationship between the non-motor manifestations of PD and degeneration of certain cortical regions of the brain.     

Systemic Interaction of the Cortical Areas during Performance of Verbal–Mnestic Activity

The dynamics of the interregional interaction of cortical areas was studied in adult test subjects who accomplished the tasks of listening to and memorizing a poem and of mental arithmetic. Analysis of the spatial and temporal relations of the oscillations of the brain biopotentials showed the participation of many regions of the left and right hemispheres in the verbal–mnestic activity. The interaction was most expressed between the posterior regions of the left hemisphere and the anterior regions of the right one. To find out whether these data agree with the classical concepts on the leading role of the left hemisphere in speech activity, the authors examined 3- and 4-year-old children with motor alalia. A comparison of 3-year-old alalics with the control group of healthy children of the same age demonstrated a marked weakening of the distant interaction of the activity of the ipsilateral antero- and posterotemporal regions of the left hemisphere (i.e., those that correspond to the Broca area and Wernicke zone) both between themselves and with the activity of other cortical regions of both hemispheres. These results confirm the important role of both the inter- and intrahemispheric relations, especially those between the Broca area and the Wernicke zone, in realizing verbal–mnestic functions. A significant weakening of the systemic interaction between EEG oscillations in these areas in alalic children suggests that the auditory feedback plays a special role during speech production in the ontogenetic development of the neurophysiological mechanisms that are responsible for speech function formation.     

fNIRS Exhibits Weak Tuning to Hand Movement Direction

Functional near-infrared spectroscopy (fNIRS) has become an established tool to investigate brain function and is, due to its portability and resistance to electromagnetic noise, an interesting modality for brain-machine interfaces (BMIs). BMIs have been successfully realized using the decoding of movement kinematics from intra-cortical recordings in monkey and human. Recently, it has been shown that hemodynamic brain responses as measured by fMRI are modulated by the direction of hand movements. However, quantitative data on the decoding of movement direction from hemodynamic responses is still lacking and it remains unclear whether this can be achieved with fNIRS, which records signals at a lower spatial resolution but with the advantage of being portable. Here, we recorded brain activity with fNIRS above different cortical areas while subjects performed hand movements in two different directions. We found that hemodynamic signals in contralateral sensorimotor areas vary with the direction of movements, though only weakly. Using these signals, movement direction could be inferred on a single-trial basis with an accuracy of ∼65% on average across subjects. The temporal evolution of decoding accuracy resembled that of typical hemodynamic responses observed in motor experiments. Simultaneous recordings with a head tracking system showed that head movements, at least up to some extent, do not influence the decoding of fNIRS signals. Due to the low accuracy, fNIRS is not a viable alternative for BMIs utilizing decoding of movement direction. However, due to its relative resistance to head movements, it is promising for studies investigating brain activity during motor experiments.     

Separation of fNIRS Signals into Functional and Systemic Components Based on Differences in Hemodynamic Modalities

In conventional functional near-infrared spectroscopy (fNIRS), systemic physiological fluctuations evoked by a body''s motion and psychophysiological changes often contaminate fNIRS signals. We propose a novel method for separating functional and systemic signals based on their hemodynamic differences. Considering their physiological origins, we assumed a negative and positive linear relationship between oxy- and deoxyhemoglobin changes of functional and systemic signals, respectively. Their coefficients are determined by an empirical procedure. The proposed method was compared to conventional and multi-distance NIRS. The results were as follows: (1) Nonfunctional tasks evoked substantial oxyhemoglobin changes, and comparatively smaller deoxyhemoglobin changes, in the same direction by conventional NIRS. The systemic components estimated by the proposed method were similar to the above finding. The estimated functional components were very small. (2) During finger-tapping tasks, laterality in the functional component was more distinctive using our proposed method than that by conventional fNIRS. The systemic component indicated task-evoked changes, regardless of the finger used to perform the task. (3) For all tasks, the functional components were highly coincident with signals estimated by multi-distance NIRS. These results strongly suggest that the functional component obtained by the proposed method originates in the cerebral cortical layer. We believe that the proposed method could improve the reliability of fNIRS measurements without any modification in commercially available instruments.     

Familiarity with speech affects cortical processing of auditory distance cues and increases acuity

Several acoustic cues contribute to auditory distance estimation. Nonacoustic cues, including familiarity, may also play a role. We tested participants' ability to distinguish the distances of acoustically similar sounds that differed in familiarity. Participants were better able to judge the distances of familiar sounds. Electroencephalographic (EEG) recordings collected while participants performed this auditory distance judgment task revealed that several cortical regions responded in different ways depending on sound familiarity. Surprisingly, these differences were observed in auditory cortical regions as well as other cortical regions distributed throughout both hemispheres. These data suggest that learning about subtle, distance-dependent variations in complex speech sounds involves processing in a broad cortical network that contributes both to speech recognition and to how spatial information is extracted from speech.     

Simulation of near-infrared light absorption considering individual head and prefrontal cortex anatomy: implications for optical neuroimaging

Functional near-infrared spectroscopy (fNIRS) is an established optical neuroimaging method for measuring functional hemodynamic responses to infer neural activation. However, the impact of individual anatomy on the sensitivity of fNIRS measuring hemodynamics within cortical gray matter is still unknown. By means of Monte Carlo simulations and structural MRI of 23 healthy subjects (mean age: 25.0±2.8 years), we characterized the individual distribution of tissue-specific NIR-light absorption underneath 24 prefrontal fNIRS channels. We, thereby, investigated the impact of scalp-cortex distance (SCD), frontal sinus volume as well as sulcal morphology on gray matter volumes (V(gray)) traversed by NIR-light, i.e. anatomy-dependent fNIRS sensitivity. The NIR-light absorption between optodes was distributed describing a rotational ellipsoid with a mean penetration depth of (23.6±0.7) mm considering the deepest 5% of light. Of the detected photon packages scalp and bone absorbed (96.4±9.7)% and V(gray) absorbed (3.1±1.8)% of the energy. The mean V(gray) volume (1.1±0.4) cm3 was negatively correlated (r=-.76) with the SCD and frontal sinus volume (r=-.57) and was reduced by 41.5% in subjects with relatively large compared to small frontal sinus. Head circumference was significantly positively correlated with the mean SCD (r=.46) and the traversed frontal sinus volume (r=.43). Sulcal morphology had no significant impact on V(gray). Our findings suggest to consider individual SCD and frontal sinus volume as anatomical factors impacting fNIRS sensitivity. Head circumference may represent a practical measure to partly control for these sources of error variance.     

A Synchrony-Dependent Influence of Sounds on Activity in Visual Cortex Measured Using Functional Near-Infrared Spectroscopy (fNIRS)

Evidence from human neuroimaging and animal electrophysiological studies suggests that signals from different sensory modalities interact early in cortical processing, including in primary sensory cortices. The present study aimed to test whether functional near-infrared spectroscopy (fNIRS), an emerging, non-invasive neuroimaging technique, is capable of measuring such multisensory interactions. Specifically, we tested for a modulatory influence of sounds on activity in visual cortex, while varying the temporal synchrony between trains of transient auditory and visual events. Related fMRI studies have consistently reported enhanced activation in response to synchronous compared to asynchronous audiovisual stimulation. Unexpectedly, we found that synchronous sounds significantly reduced the fNIRS response from visual cortex, compared both to asynchronous sounds and to a visual-only baseline. It is possible that this suppressive effect of synchronous sounds reflects the use of an efficacious visual stimulus, chosen for consistency with previous fNIRS studies. Discrepant results may also be explained by differences between studies in how attention was deployed to the auditory and visual modalities. The presence and relative timing of sounds did not significantly affect performance in a simultaneously conducted behavioral task, although the data were suggestive of a positive relationship between the strength of the fNIRS response from visual cortex and the accuracy of visual target detection. Overall, the present findings indicate that fNIRS is capable of measuring multisensory cortical interactions. In multisensory research, fNIRS can offer complementary information to the more established neuroimaging modalities, and may prove advantageous for testing in naturalistic environments and with infant and clinical populations.     

Electric Field Encephalography as a Tool for Functional Brain Research: A Modeling Study

We introduce the notion of Electric Field Encephalography (EFEG) based on measuring electric fields of the brain and demonstrate, using computer modeling, that given the appropriate electric field sensors this technique may have significant advantages over the current EEG technique. Unlike EEG, EFEG can be used to measure brain activity in a contactless and reference-free manner at significant distances from the head surface. Principal component analysis using simulated cortical sources demonstrated that electric field sensors positioned 3 cm away from the scalp and characterized by the same signal-to-noise ratio as EEG sensors provided the same number of uncorrelated signals as scalp EEG. When positioned on the scalp, EFEG sensors provided 2–3 times more uncorrelated signals. This significant increase in the number of uncorrelated signals can be used for more accurate assessment of brain states for non-invasive brain-computer interfaces and neurofeedback applications. It also may lead to major improvements in source localization precision. Source localization simulations for the spherical and Boundary Element Method (BEM) head models demonstrated that the localization errors are reduced two-fold when using electric fields instead of electric potentials. We have identified several techniques that could be adapted for the measurement of the electric field vector required for EFEG and anticipate that this study will stimulate new experimental approaches to utilize this new tool for functional brain research.     

Identification of the Pain Process by Cold Stimulation: Using Dynamic Causal Modeling of Effective Connectivity in Functional Near-Infrared Spectroscopy (fNIRS)

Background

Pain is an unpleasant sensory and emotional experience followed by anxiety, depression, and frustration. Functional Near-Infrared Spectroscopy (fNIRS) as an optical technique identifies the brain functional networks by investigating connectivity between functionally linked of different anatomical regions in response to pain stimulation.

Cortical asymmetries at different spatial hierarchies relate to phonological processing ability

The ability to map speech sounds to corresponding letters is critical for establishing proficient reading. People vary in this phonological processing ability, which has been hypothesized to result from variation in hemispheric asymmetries within brain regions that support language. A cerebral lateralization hypothesis predicts that more asymmetric brain structures facilitate the development of foundational reading skills like phonological processing. That is, structural asymmetries are predicted to linearly increase with ability. In contrast, a canalization hypothesis predicts that asymmetries constrain behavioral performance within a normal range. That is, structural asymmetries are predicted to quadratically relate to phonological processing, with average phonological processing occurring in people with the most asymmetric structures. These predictions were examined in relatively large samples of children (N = 424) and adults (N = 300), using a topological asymmetry analysis of T1-weighted brain images and a decoding measure of phonological processing. There was limited evidence of structural asymmetry and phonological decoding associations in classic language-related brain regions. However, and in modest support of the cerebral lateralization hypothesis, small to medium effect sizes were observed where phonological decoding accuracy increased with the magnitude of the largest structural asymmetry across left hemisphere cortical regions, but not right hemisphere cortical regions, for both the adult and pediatric samples. In support of the canalization hypothesis, small to medium effect sizes were observed where phonological decoding in the normal range was associated with increased asymmetries in specific cortical regions for both the adult and pediatric samples, which included performance monitoring and motor planning brain regions that contribute to oral and written language functions. Thus, the relevance of each hypothesis to phonological decoding may depend on the scale of brain organization.     

Communicative signaling activates 'Broca's' homolog in chimpanzees

Broca's area, a cerebral cortical area located in the inferior frontal gyrus (IFG) of the human brain, has been identified as one of several critical regions associated with the motor planning and execution of language. Anatomically, Broca's area is most often larger in the left hemisphere, and functional imaging studies in humans indicate significant left-lateralized patterns of activation during language-related tasks. If, and to what extent, nonhuman primates, particularly chimpanzees, possess a homologous region that is involved in the production of their own communicative signals remains unknown. Here, we show that portions of the IFG as well as other cortical and subcortical regions in chimpanzees are active during the production of communicative signals. These findings are the first to provide direct evidence of the neuroanatomical structures associated with the production of communicative behaviors in chimpanzees. Significant activation in the left IFG in conjunction with other cortical and subcortical brain areas during the production of communicative signals in chimpanzees suggests that the neurological substrates underlying language production in the human brain may have been present in the common ancestor of humans and chimpanzees.     

Normal neuroanatomical variation in the human brain: an MRI-volumetric study

Normative data on the in vivo size of the human brain and its major anatomically defined subdivisions are not readily available. In this study, high-resolution magnetic resonance imaging was used to measure regional brain volumes in 46 normal, right-handed adults (23 men, 23 women) between the ages of 22-49 years. Parcellation of the brain was based on neuroanatomical landmarks. The following brain regions were measured: the cerebral hemispheres, frontal lobe, temporal lobe, parietal lobe, occipital lobe, cingulate gyrus, insula, cerebellum, corpus callosum, and lateral ventricles. Males tend to be significantly larger than females, for the whole brain and for nearly all of its major subdivisions, including the corpus callosum. However, the proportional sizes of regions relative to total volume of the hemisphere are remarkably similar in males and females. Variation in size of region is always greater than variation in proportional representation. Asymmetries in brain regions are not profound, with the exception of the cingulate gyrus, which is larger in the left hemisphere. Brain regions are highly correlated in size, with the exception of the lateral ventricles. After controlling for hemisphere size, the volumes of the frontal and parietal lobes are significantly negatively correlated. The occipital lobe tends to be less sexually dimorphic than other major lobes, and less correlated with other brain regions for volume. These results have implications for understanding whether or not certain sectors of the brain have shown relative expansion over the course of hominid and hominoid evolution.     

Alterations in Cortical Morphology after Neonatal Stroke: Compensation in the Contralesional Hemisphere?

Although neonatal arterial ischemic stroke is now well‐studied, its complex consequences on long‐term cortical brain development has not yet been solved. In order to understand the brain development after focal early brain lesion, brain morphometry needs to be evaluated using structural parameters. In this work, our aim was to study and analyze the changes in morphometry of ipsi‐ and contralesional hemispheres in seven‐year‐old children following neonatal stroke. Therefore, we used surface‐based morphometry in order to examine the cortical thickness, surface area, cortical volume, and local gyrification index in two groups of children that suffered from neonatal stroke in the left (n = 19) and right hemispheres (n = 15) and a group of healthy controls (n = 30). Reduced cortical thickness, surface area, and cortical volumes were observed in the ipsilesional hemispheres for both groups in comparison with controls. For the group with left‐sided lesions, higher gyrification of the contralesional hemisphere was observed primarily in the occipital region along with higher surface area and cortical volume. As for the group with right‐sided lesions, higher gyrification was detected in two separate clusters also in the occipital lobe of the contralesional hemisphere, without a significant change in cortical thickness, surface area, or cortical volume. This is the first time that alterations of structural parameters are detected in the “healthy” hemisphere after unilateral neonatal stroke indicative of a compensatory phenomenon. Moreover, findings presented in this work suggest that lesion lateralization might have an influence on brain development and maturation.     

Hemodynamic changes in cortical sensorimotor systems following hand and orofacial motor tasks and pulsed pneumotactile stimulation

We performed a functional near-infrared spectroscopy (fNIRS) study of the evoked hemodynamic responses seen in hand and face sensorimotor cortical representations during (1) active motor tasks and (2) pulsed pneumotactile stimulation. Contralateral fNIRS measurements were performed on 22 healthy adult participants using a block paradigm that consisted of repetitive right hand and right oral angle somatosensory stimulation using a pulsed pneumotactile array stimulator, and repetitive right-hand grip compression and bilabial compressions on strain gages. Results revealed significant oxyhemoglobin (HbO) modulation across stimulus conditions in corresponding somatotopic cortical regions. Of the 22 participants, 86% exhibited a decreased HbO response during at least one of the stimulus conditions, which may be indicative of cortical steal, or hypo-oxygenation occurring in channels adjacent to the primary areas of activation. Across all conditions, 56% of participants’ HbO responses were positive and 44% were negative. Hemodynamic responses most likely differed across hand and face motor and somatosensory cortical regions due to differences in regional arterial/venous anatomy, cortical vascular beds, extent and orientation of somatotopy, task dynamics, and mechanoreceptor typing in hand and face. The combination of optical imaging and task conditions allowed for non-invasive examination of hemodynamic changes in somatosensory and motor cortices using natural, pneumatic stimulation of glabrous hand and hairy skin of the lower face and functionally relevant and measurable motor tasks involving the same structures.     

Reduced Cortical Complexity in Children with Prader-Willi Syndrome and Its Association with Cognitive Impairment and Developmental Delay

Background

Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group.

Methods

High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite.

Results

Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ.

Conclusions

These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene networks that play a prominent role in early brain development.     

Maturation of the language network: from inter- to intrahemispheric connectivities

Language development must go hand-in-hand with brain maturation. Little is known about how the brain develops to serve language processing, in particular, the processing of complex syntax, a capacity unique to humans. Behavioral reports indicate that the ability to process complex syntax is not yet adult-like by the age of seven years. Here, we apply a novel method to demonstrate that the basic neural basis of language, as revealed by low frequency fluctuation stemming from functional MRI data, differs between six-year-old children and adults in crucial aspects. Although the classical language regions are actively in place by the age of six, the functional connectivity between these regions clearly is not. In contrast to adults who show strong connectivities between frontal and temporal language regions within the left hemisphere, children's default language network is characterized by a strong functional interhemispheric connectivity, mainly between the superior temporal regions. These data indicate a functional reorganization of the neural network underlying language development towards a system that allows a close interplay between frontal and temporal regions within the left hemisphere.     

Atlas-free surface reconstruction of the cortical grey-white interface in infants

Background

The segmentation of the cortical interface between grey and white matter in magnetic resonance images (MRI) is highly challenging during the first post-natal year. First, the heterogeneous brain maturation creates important intensity fluctuations across regions. Second, the cortical ribbon is highly folded creating complex shapes. Finally, the low tissue contrast and partial volume effects hamper cortex edge detection in parts of the brain.

Methods and Findings

We present an atlas-free method for segmenting the grey-white matter interface of infant brains in T2-weighted (T2w) images. We used a broad characterization of tissue using features based not only on local contrast but also on geometric properties. Furthermore, inaccuracies in localization were reduced by the convergence of two evolving surfaces located on each side of the inner cortical surface. Our method has been applied to eleven brains of one- to four-month-old infants. Both quantitative validations against manual segmentations and sulcal landmarks demonstrated good performance for infants younger than two months old. Inaccuracies in surface reconstruction increased with age in specific brain regions where the tissue contrast decreased with maturation, such as in the central region.

Conclusions

We presented a new segmentation method which achieved good to very good performance at the grey-white matter interface depending on the infant age. This method should reduce manual intervention and could be applied to pathological brains since it does not require any brain atlas.     

Abnormal cortical networks in mild cognitive impairment and Alzheimer's disease

Recently, many researchers have used graph theory to study the aberrant brain structures in Alzheimer's disease (AD) and have made great progress. However, the characteristics of the cortical network in Mild Cognitive Impairment (MCI) are still largely unexplored. In this study, the gray matter volumes obtained from magnetic resonance imaging (MRI) for all brain regions except the cerebellum were parcellated into 90 areas using the automated anatomical labeling (AAL) template to construct cortical networks for 98 normal controls (NCs), 113 MCIs and 91 ADs. The measurements of the network properties were calculated for each of the three groups respectively. We found that all three cortical networks exhibited small-world properties and those strong interhemispheric correlations existed between bilaterally homologous regions. Among the three cortical networks, we found the greatest clustering coefficient and the longest absolute path length in AD, which might indicate that the organization of the cortical network was the least optimal in AD. The small-world measures of the MCI network exhibited intermediate values. This finding is logical given that MCI is considered to be the transitional stage between normal aging and AD. Out of all the between-group differences in the clustering coefficient and absolute path length, only the differences between the AD and normal control groups were statistically significant. Compared with the normal controls, the MCI and AD groups retained their hub regions in the frontal lobe but showed a loss of hub regions in the temporal lobe. In addition, altered interregional correlations were detected in the parahippocampus gyrus, medial temporal lobe, cingulum, fusiform, medial frontal lobe, and orbital frontal gyrus in groups with MCI and AD. Similar to previous studies of functional connectivity, we also revealed increased interregional correlations within the local brain lobes and disrupted long distance interregional correlations in groups with MCI and AD.     

Correlations among brain gray matter volumes, age, gender, and hemisphere in healthy individuals

To determine the relationship between age and gray matter structure and how interactions between gender and hemisphere impact this relationship, we examined correlations between global or regional gray matter volume and age, including interactions of gender and hemisphere, using a general linear model with voxel-based and region-of-interest analyses. Brain magnetic resonance images were collected from 1460 healthy individuals aged 20-69 years; the images were linearly normalized and segmented and restored to native space for analysis of global gray matter volume. Linearly normalized images were then non-linearly normalized and smoothed for analysis of regional gray matter volume. Analysis of global gray matter volume revealed a significant negative correlation between gray matter ratio (gray matter volume divided by intracranial volume) and age in both genders, and a significant interaction effect of age × gender on the gray matter ratio. In analyzing regional gray matter volume, the gray matter volume of all regions showed significant main effects of age, and most regions, with the exception of several including the inferior parietal lobule, showed a significant age × gender interaction. Additionally, the inferior temporal gyrus showed a significant age × gender × hemisphere interaction. No regional volumes showed significant age × hemisphere interactions. Our study may contribute to clarifying the mechanism(s) of normal brain aging in each brain region.