Cortical processing of musical pitch as reflected by behavioural and electrophysiological evidence

In a musical context, the pitch of sounds is encoded according to domain-general principles not confined to music or even to audition overall but common to other perceptual and cognitive processes (such as multiple pattern encoding and feature integration), and to domain-specific and culture-specific properties related to a particular musical system only (such as the pitch steps of the Western tonal system). The studies included in this thesis shed light on the processing stages during which pitch encoding occurs on the basis of both domain-general and music-specific properties, and elucidate the putative brain mechanisms underlying pitch-related music perception. Study I showed, in subjects without formal musical education, that the pitch and timbre of multiple sounds are integrated as unified object representations in sensory memory before attentional intervention. Similarly, multiple pattern pitches are simultaneously maintained in non-musicians' sensory memory (Study II). These findings demonstrate the degree of sophistication of pitch processing at the sensory memory stage, requiring neither attention nor any special expertise of the subjects. Furthermore, music- and culture-specific properties, such as the pitch steps of the equal-tempered musical scale, are automatically discriminated in sensory memory even by subjects without formal musical education (Studies III and IV). The cognitive processing of pitch according to culture-specific musical-scale schemata hence occurs as early as at the sensory-memory stage of pitch analysis. Exposure and cortical plasticity seem to be involved in musical pitch encoding. For instance, after only one hour of laboratory training, the neural representations of pitch in the auditory cortex are altered (Study V). However, faulty brain mechanisms for attentive processing of fine-grained pitch steps lead to inborn deficits in music perception and recognition such as those encountered in congenital amusia (Study VI). These findings suggest that predispositions for exact pitch-step discrimination together with long-term exposure to music govern the acquisition of the automatized schematic knowledge of the music of a particular culture that even non-musicians possess.

Cortical representations for phonological quantity

Different languages use temporal speech cues in different linguistic functions. In Finnish, speech-sound duration is used as the primary cue for the phonological quantity distinction ― i.e., a distinction between short and long phonemes. For the second-language (L2) learners of Finnish, quantity is often difficult to master if speech-sound duration plays a less important role in the phonology of their native language (L1). The present studies aimed to investigate the cortical representations for phonological quantity in native speakers and L2 users of Finnish by using behavioral and electrophysiological methods. Since long-term memory representations for different speech units have been previously shown to participate in the elicitation of the mismatch negativity (MMN) brain response, MMN was used to compare the neural representation for quantity between native speakers and L2 users of Finnish. The results of the studies suggested that native Finnish speakers' MMN response to quantity was determined by the activation of native-language phonetic prototypes rather than by phoneme boundaries. In addition, native speakers seemed to process phoneme quantity and quality independently from each other by separate brain representations. The cross-linguistic MMN studies revealed that, in native speakers of Finnish, the MMN response to duration or quantity-degree changes was enhanced in amplitude selectively in speech sounds, whereas this pattern was not observed in L2 users. Native speakers' MMN enhancement is suggested to be due to the pre-attentive activation of L1 prototypes for quantity. In L2 users, the activation of L2 prototypes or other L2 learning effects were not reflected in the MMN, with one exception. Even though L2 users failed to show native-like brain responses to duration changes in a vowel that was similar in L1 and L2, their duration MMN response was native-like for an L2 vowel with no counterpart in L1. Thus, the pre-attentive activation of L2 users' representations was determined by the degree of similarity of L2 sounds to L1 sounds. In addition, behavioral experiments suggested that the establishment of representations for L2 quantity may require several years of language exposure.

Effects of increasing neuromuscular electrical stimulation current intensity on cortical sensorimotor network activation: A time domain fNIRS study

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O₂Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O₂Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O₂Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

A new methodology for realizing magnification of holographic images

The article describes a new method for obtaining a holographic image of desired magnification, consistent with the stipulated criteria for its resolution and aberrations.

Neuromagnetic studies on cortical somatosensory functions in infants and children : Normal development and effect of early brain lesions

Until recently, objective investigation of the functional development of the human brain in vivo was challenged by the lack of noninvasive research methods. Consequently, fairly little is known about cortical processing of sensory information even in healthy infants and children. Furthermore, mechanisms by which early brain insults affect brain development and function are poorly understood. In this thesis, we used magnetoencephalography (MEG) to investigate development of cortical somatosensory functions in healthy infants, very premature infants at risk for neurological disorders, and adolescents with hemiplegic cerebral palsy (CP). In newborns, stimulation of the hand activated both the contralateral primary (SIc) and secondary somatosensory cortices (SIIc). The activation patterns differed from those of adults, however. Some of the earliest SIc responses, constantly present in adults, were completely lacking in newborns and the effect of sleep stage on SIIc responses differed. These discrepancies between newborns and adults reflect the still developmental stage of the newborns’ somatosensory system. Its further maturation was demonstrated by a systematic transformation of the SIc response pattern with age. The main early adult­like components were present by age two. In very preterm infants, at term age, the SIc and SIIc were activated at similar latencies as in healthy fullterm newborns, but the SIc activity was weaker in the preterm group. The SIIc response was absent in four out of the six infants with brain lesions of the underlying hemisphere. Determining the prognostic value of this finding remains a subject for future studies, however. In the CP adolescents with pure subcortical lesions, contrasting their unilateral symptoms, the SIc responses of both hemispheres differed from those of controls: For example the distance between SIc representation areas for digits II and V was shorter bilaterally. In four of the five CP patients with cortico­subcortical brain lesions, no normal early SIc responses were evoked by stimulation of the palsied hand. The varying differences in neuronal functions, underlying the common clinical symptoms, call for investigation of more precisely designed rehabilitation strategies resting on knowledge about individual functional alterations in the sensorimotor networks.

Heritability analysis of surface-based cortical thickness estimation on a large twin cohort

The aim of this paper is to assess the heritability of cerebral cortex, based on measurements of grey matter (GM) thickness derived from structural MR images (sMRI). With data acquired from a large twin cohort (328 subjects), an automated method was used to estimate the cortical thickness, and EM-ICP surface registration algorithm was used to establish the correspondence of cortex across the population. An ACE model was then employed to compute the heritability of cortical thickness. Heritable cortical thickness measures various cortical regions, especially in frontal and parietal lobes, such as bilateral postcentral gyri, superior occipital gyri, superior parietal gyri, precuneus, the orbital part of the right frontal gyrus, right medial superior frontal gyrus, right middle occipital gyrus, right paracentral lobule, left precentral gyrus, and left dorsolateral superior frontal gyrus.

Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations

Primary microcephaly is an autosomal recessive disorder characterized by smaller than normal brain size and mental retardation. It is genetically heterogeneous with seven loci: MCPH1-MCPH7. We have previously reported genetic analysis of 35 families, including the identification of the MCPH7 gene STIL. Of the 35 families, three families showed linkage to the MCPH2 locus. Recent whole-exome sequencing studies have shown that the WDR62 gene, located in the MCPH2 candidate region, is mutated in patients with severe brain malformations. We therefore sequenced the WDR62 gene in our MCPH2 families and identified two novel homozygous protein truncating mutations in two families. Affected individuals in the two families had pachygyria, microlissencephaly, band heterotopias, gyral thickening, and dysplastic cortex. Using immunofluorescence study, we showed that, as with other MCPH proteins, WDR62 localizes to centrosomes in A549, HepG2, and HaCaT cells. In addition, WDR62 was also localized to nucleoli. Bioinformatics analysis predicted two overlapping nuclear localization signals and multiple WD-40 repeats in WDR62. Two other groups have also recently identified WDR62 mutations in MCPH2 families. Our results therefore add further evidence that WDR62 is the MCPH2 gene. The present findings will be helpful in genetic diagnosis of patients linked to the MCPH2 locus.

Reach task-associated excitatory overdrive of motor cortical neurons following infusion with ALS-CSF

Converging evidence from transgenic animal models of amyotrophic lateral sclerosis (ALS) and human studies suggest alterations in excitability of the motor neurons in ALS. Specifically, in studies on human subjects with ALS the motor cortex was reported to be hyperexcitable. The present study was designed to test the hypothesis that infusion of cerebrospinal fluid from patients with sporadic ALS (ALS-CSF) into the rat brain ventricle can induce hyperexcitability and structural changes in the motor cortex leading to motor dysfunction. A robust model of sporadic ALS was developed experimentally by infusing ALS-CSF into the rat ventricle. The effects of ALS-CSF at the single neuron level were examined by recording extracellular single unit activity from the motor cortex while rats were performing a reach to grasp task. We observed an increase in the firing rate of the neurons of the motor cortex in rats infused with ALS-CSF compared to control groups. This was associated with impairment in a specific component of reach with alterations in the morphological characteristics of the motor cortex. It is likely that the increased cortical excitability observed in the present study could be the result of changes in the intrinsic properties of motor cortical neurons, a dysfunctional inhibitory mechanism and/or an underlying structural change culminating in a behavioral deficit.

High resolution cortical bone thickness measurement from clinical CT data.

The distribution of cortical bone in the proximal femur is believed to be a critical component in determining fracture resistance. Current CT technology is limited in its ability to measure cortical thickness, especially in the sub-millimetre range which lies within the point spread function of today's clinical scanners. In this paper, we present a novel technique that is capable of producing unbiased thickness estimates down to 0.3mm. The technique relies on a mathematical model of the anatomy and the imaging system, which is fitted to the data at a large number of sites around the proximal femur, producing around 17,000 independent thickness estimates per specimen. In a series of experiments on 16 cadaveric femurs, estimation errors were measured as -0.01+/-0.58mm (mean+/-1std.dev.) for cortical thicknesses in the range 0.3-4mm. This compares with 0.25+/-0.69mm for simple thresholding and 0.90+/-0.92mm for a variant of the 50% relative threshold method. In the clinically relevant sub-millimetre range, thresholding increasingly fails to detect the cortex at all, whereas the new technique continues to perform well. The many cortical thickness estimates can be displayed as a colour map painted onto the femoral surface. Computation of the surfaces and colour maps is largely automatic, requiring around 15min on a modest laptop computer.