The early months of stuttering: a developmental study

Objective data on the development of stuttering during its first several months are sparse. Such a deficit is due to parents' tendency to postpone professional consultation regarding early stuttering until later in the course of the disorder and to a lack of longitudinal studies beginning close to onset. This report presents information on a rare group of 16 preschool subjects who were evaluated within several weeks after stuttering onset and followed for 6 months using multiple measures. The findings show that often early stuttering takes on a moderate-to-severe form. Substantial changes occurred, however, during the 6 months of the study, with a strong tendency for reduction in stuttering-like disfluencies, number of head/face movements, clinician severity ratings of stuttering, and parent ratings of stuttering. Several subjects, including severe cases, exhibited complete recovery. The large changes that occur during the early stage of stuttering suggest that relatively small differences in the length of post-onset interval (stuttering history) can greatly influence all research data of early childhood stuttering. The high, as well as fast, improvement rate suggests that the precise timing of early intervention should be conscientiously evaluated in carefully controlled studies.     

A neural systems theory of schizophrenia and tardive dyskinesia

Some systems ideas applied to individual persons are used to try to explain symptoms of schizophrenia and a syndrome of uncontrolled fragments of movement which sometimes occurs as a side effect of chronic, antipsychotic drug therapy. The behavior of normal organisms may be conceptualized in three echelons of control, with each successively higher echelon organizing, by selective disinhibition, semiautonomous, spontaneous fragments of activity which comprise the next lower echelon. It is hypothesized that schizophrenia involves a deficiency of inhibition by the frontal cortex, first echelon, on the corpus striatum, second echelon. This results first in insufficiently integrated fragments of behavior, and second in premature associative linkages among active elements. First echelon control develops as a normal person matures and gradually loses some of the playful activities of childhood. It is hypothesized that by disrupting certain aspects of activity in the corpus striatum, neuroleptic drugs reduce schizophrenic symptoms but also reduce the capacity of the second echelon to inhibit and integrate the smaller behavioral fragments wired into lower parts of the brain, third echelon. This results in uncontrolled movements. Though many researchers already favor the hypothesis that neuroleptic drugs act on the corpus striatum, the broader theory presented here is new and depends in large part on general living systems considerations. Emphasis is on conceptual decomposition of the integrated behavior of a whole organism into less complex subsystems. Individually, these have neither too much nor too little complexity to yield a plausible model. Some experimental predictions and predictions about possible therapies are made from the theory.     

Distributed neural systems underlying the timing of movements

Timing is essential to the execution of skilled movements, yet our knowledge of the neural systems underlying timekeeping operations is limited. Using whole-brain functional magnetic resonance imaging, subjects were imaged while tapping with their right index finger in synchrony with tones that were separated by constant intervals [Synchronization (S)], followed by tapping without the benefit of an auditory cue [Continuation (C)]. Two control conditions followed in which subjects listened to tones and then made pitch discriminations (D). Both the S and the C conditions produced equivalent activation within the left sensorimotor cortex, the right cerebellum (dorsal dentate nucleus), and the right superior temporal gyrus (STG). Only the C condition produced activation of a medial premotor system, including the caudal supplementary motor area (SMA), the left putamen, and the left ventrolateral thalamus. The C condition also activated a region within the right inferior frontal gyrus (IFG), which is functionally interconnected with auditory cortex. Both control conditions produced bilateral activation of the STG, and the D condition also activated the rostral SMA. These results suggest that the internal generation of precisely timed movements is dependent on three interrelated neural systems, one that is involved in explicit timing (putamen, ventrolateral thalamus, SMA), one that mediates auditory sensory memory (IFG, STG), and another that is involved in sensorimotor processing (dorsal dentate nucleus, sensorimotor cortex).     

Bethanechol in the treatment of stuttering

A double-blind trial of bethanechol for the treatment of stuttering that used a crossover experimental design failed to find the drug superior to placebo. However, two of the patients who did respond favorably elected to continue with the medication and have remained more fluent after taking the drug for 6 months. The notion of "bethanechol responders" is advanced.     

Temporal dynamics of repetitions during the early stage of childhood stuttering: an acoustic study

The purpose of this study was to compare duration characteristics of single-syllable whole-word repetitions (with one and two repeated units) and part-word repetitions (with one repeated unit) in the speech of preschool children who stutter (N = 20) recorded near the onset of their stuttering to those of control nonstuttering children (N = 20). Disfluent episodes were identified in audiotape recordings of the subjects' conversational speech. The digitized signals were analyzed by means of the CSpeech computer software (Milenkovic, 1987). Using visual displays of sound spectrograms, the durations of the spoken repetition unit(s), the silent interval(s) between the units, and the total disfluency were measured. The stutters exhibited shorter silent intervals between spoken repetition units. The duration of the spoken repetition units was very similar for the two groups of children. The total duration of the stutterers' disfluencies was significantly shorter because of their shorter silent intervals when compared to disfluencies of equal repetition units produced by the control subjects. Statistical analysis revealed that silent interval duration was capable of differentiating stuttering from normally fluent children with 72-87% accuracy, dependent upon the disfluency type. To the degree that the groups of subjects represented random samples of the two specified populations from which they were drawn, there appears to be an overall tendency for repetitions during the early stage of stuttering to be produced at a faster rate than repetitions produced by nonstuttering children.     

A comparative morphological study of homo- and heterotopic neural transplants

A comparative study of the development of neocortex embryonal anlage was carried out using light and electron microscopy in 15 days Wistar-line rat embryo after its transplantation into the brain and disturbed sciatic nerve of mature rats. Homotopic transplants contained twice more neurons than heterotopic ones 30 days later. Unlike to intracerebral transplants, in grafts developing in the nerve, there forms a multilayer lining from ependymocytes on the border with recipient tissue. Microenvironment was suggested to influence the realization of the transferred cells precursors histoblastic properties.     

A note on vowel centralization in stuttering and nonstuttering individuals

Inferences were made regarding vocal tract vowel space during fluently produced utterances through examination of the first two formant frequencies. Fifteen adult males served as subjects, representing separate groups of untreated and treated individuals who stutter and nonstuttering controls. The steady-state portion of formant one (F1) and formant two (F2) was examined in the production of various CVC tokens containing the vowels /i/, /u/, and /a/. Vocal tract vowel space was estimated three ways. The first analysis scheme involved measurement of formant frequency spacing. The second measure involved calculating the area of the vowel space triangle. The third measure was based on calculating the average Euclidean distance from each subject's midpoint "centroid" vocal tract position to the corresponding /i/, /u/, and /a/ points on the vowel triangle. The formant frequency spacing measures proved to be most revealing of group differences, with the untreated stutterers showing significantly greater vowel centralization than the treated group and control group. Discussion focuses on the vocal tract articulation characterizing fluent speech productions and possible treatment implications for persons who stutter.     

Multiple receptor systems promote CNS neural migration

To identify glial receptor systems in CNS migration, cerebellar granule neuron migration was assayed on glass fibers coated with polylysine, astroglial membranes (AM fibers), or the extracellular matrix proteins collagen (COLL fibers), fibronectin (FN fibers), and laminin (LAM fibers). By video microscopy, granule cells migrated along AM fibers with the cytology, neuron-fiber apposition, and dynamics seen on living glia. The demonstration that immobilized astroglial membranes support neural migration suggests that astroglial receptor systems, in combination with glial fiber geometry, promote CNS neural migration. Moreover, granule neurons migrated rapidly on LAM fibers, moved relatively slowly on FN fibers, and not at all on COLL fibers. Antibody perturbation analyses suggested that, whereas astrotactin provides the neural receptor for migration on astroglial membranes, integrin beta 1 provides the neural receptor for migration on LAM fibers. These results suggest that multiple receptor systems support CNS neural migration.     

A 15O-H2O PET study of meditation and the resting state of normal consciousness

The aim of the present study was to examine whether the neural structures subserving meditation can be reproducibly measured, and, if so, whether they are different from those supporting the resting state of normal consciousness. Cerebral blood flow distribution was investigated with the 15O-H20 PET technique in nine young adults, who were highly experienced yoga teachers, during the relaxation meditation (Yoga Nidra), and during the resting state of normal consciousness. In addition, global CBF was measured in two of the subjects. Spectral EEG analysis was performed throughout the investigations. In meditation, differential activity was seen, with the noticeable exception of V1, in the posterior sensory and associative cortices known to participate in imagery tasks. In the resting state of normal consciousness (compared with meditation as a baseline), differential activity was found in dorso-lateral and orbital frontal cortex, anterior cingulate gyri, left temporal gyri, left inferior parietal lobule, striatal and thalamic regions, pons and cerebellar vermis and hemispheres, structures thought to support an executive attentional network. The mean global flow remained unchanged for both subjects throughout the investigation (39+/-5 and 38+/-4 ml/100 g/min, uncorrected for partial volume effects). It is concluded that the (H2)15O PET method may measure CBF distribution in the meditative state as well as during the resting state of normal consciousness, and that characteristic patterns of neural activity support each state. These findings enhance our understanding of the neural basis of different aspects of consciousness.     

A role for the hippocampal formation in implicit memory: a 3-D PET study

The apparent preservation of word priming effects in amnesia has been interpreted as supporting the view that implicit memory depends on brain systems that are independent of mesial temporal lobe structures which are in part responsible for explicit memory disorders. Nevertheless, a number of studies have demonstrated word priming deficits in amnesic patients relatively to normal subjects, suggesting that such structures may also be involved in implicit memory. To determine whether one such structure, the hippocampal formation, is a component of the brain system subserving word priming, a 3-D PET study was carried out in 13 normal individuals. Encoding was carried out using the brief multiple presentation technique, a procedure that allows one to effectively circumvent contamination of implicit memory tasks by explicit memory strategies. Results revealed that word priming was indeed associated with an activation of the right hippocampal formation. This finding of an hippocampal involvement in word priming calls into question the notion of absolute dissociability between the brain systems underlying performance on various explicit and implicit memory tasks.     

Where and when to pay attention: the neural systems for directing attention to spatial locations and to time intervals as revealed by both PET and fMRI

Although attention is distributed across time as well as space, the temporal allocation of attention has been less well researched than its spatial counterpart. A temporal analog of the covert spatial orientation task [Posner MI, Snyder CRR, Davidson BJ (1980) Attention and the detection of signals. J Exp Psychol Gen 109:160-174] was developed to compare the neural systems involved in directing attention to spatial locations versus time intervals. We asked whether there exists a general system for allocating attentional resources, independent of stimulus dimension, or whether functionally specialized brain regions are recruited for directing attention toward spatial versus temporal aspects of the environment. We measured brain activity in seven healthy volunteers by using positron emission tomography (PET) and in eight healthy volunteers by using functional magnetic resonance imaging (fMRI). The task manipulated cued attention to spatial locations (S) and temporal intervals (T) in a factorial design. Symbolic central cues oriented subjects toward S only (left or right), toward T only (300 msec or 1500 msec), toward both S and T simultaneously, or provided no information regarding S or T. Subjects also were scanned during a resting baseline condition. Behavioral data showed benefits and costs for performance during temporal attention similar to those established for spatial attention. Brain-imaging data revealed a partial overlap between neural systems involved in the performance of spatial versus temporal orientation of attention tasks. Additionally, hemispheric asymmetries revealed preferential right and left parietal activation for spatial and temporal attention, respectively. Parietal cortex was activated bilaterally by attending to both dimensions simultaneously. This is the first direct comparison of the neural correlates of attending to spatial versus temporal cues.     

A PET study of Turner's syndrome: effects of sex steroids and the X chromosome on brain

Women with Turner's syndrome (TS) allow us to study the neurobiological associates of cognitive and behavioral abnormalities because they lack one/part of one X chromosome, and endogenous estrogen. We studied 13 healthy controls (mean age +/- SD, 28 +/- 6 years) and 16 TS subjects (mean age +/- SD, 26 +/- 6 years). We measured cognitive abilities using neuropsychological tests, and cerebral metabolic rates for glucose with positron emission tomography. Compared to controls, TS subjects had significant absolute hypermetabolism in most brain areas; however, normalized metabolism was significantly lower in TS subjects than controls in the insula and association neocortices bilaterally, and there were significant differences in functional metabolic associations of brain region pairs originating in occipital cortex bilaterally, and within the right hemisphere. There were significant correlations between right-left cognitive and metabolic asymmetries in the TS group. Also, within TS a preliminary analysis demonstrated "X chromosome dosage" effects in language ability and left temporal metabolism, asymmetry of right-left test scores, and parietal metabolism. We hypothesize that within TS: i) generalized brain hypermetabolism reflects global abnormalities in neuron packing; ii) neuronal abnormalities occur in association neocortex that differ in nature or extent from whole brain and are associated with significant differences in normalized metabolism; iii) cognitive deficits are related to brain metabolic abnormalities; and iv) social-behavioral problems may be related to abnormalities of brain metabolism. Moreover, in human brain the X chromosome involved in development of the association neocortices.     

Factors contributing to the reduction of stuttering during singing

This study was conducted to determine if the reduction of stuttering typically observed during singing is associated with altered vocalization or the familiarity of the melody and lyrics of the song sung by the stutterer, or both. Subjects were eight adult male stutterers. Prior to testing, each of these individuals demonstrated that he knew the melody and lyrics of a well-known song from memory. Subsequently, subjects were asked to read these lyrics aloud and then sing them. Next, subjects had to read aloud and then sing a set of unfamiliar lyrics to the conventional melody of the same song. The stutterers' reading and singing performances were audiotaped. The dependent measures of utterance duration and stuttering frequency were extracted from the tapes. Results showed that subjects' utterance durations were significantly longer during singing than reading. The main effects of singing and familiarity were both associated with significant reductions in stuttering frequency. The greatest decrement in stuttering occurred in the condition where subjects sang the familiar melody and lyrics. These findings were interpreted to mean that changes in vocalization cannot account for all of the decrease in stuttering that occurs during singing. During song, the familiarity of the melody and lyrics being produced may also affect stuttering frequency.     

Parents as partners in the treatment of childhood stuttering

Speech-language pathologists involved in treating childhood stuttering have increasingly emphasized the need for parental involvement in intervention. In this article, we review prevailing theoretical models of stuttering and illustrate various ways in which these models can be used to guide practitioners in determining how best to include parents in intervention. We argue that successful parental involvement depends upon the ability of parents and clinicians to reach consensus on issues such as the parents' role in the onset and development of stuttering, the rationale for including parents in fluency intervention, and the importance early intervention. The article concludes with a discussion of specific ways that parents can assist in intervention through modeling, managing conversational pace and complexity, and, in some cases, directly instructing their children.     

Interactions of cholinergic and glutamatergic neuronal systems in the functional activation of cerebral blood flow response: a PET study in unanesthetized monkeys

The present study investigated the effects of the NMDA receptor antagonists dizocilpine (MK-801) and ifenprodil on the appearance of diazepam withdrawal signs caused by discontinuation of long-term diazepam treatment using a drug-admixed food (DAF) method in Fischer 344 rats. The total withdrawal score was significantly decreased by after-withdrawal treatment with dizocilpine or ifenprodil. Dizocilpine, in particular, markedly suppressed the motor withdrawal signs and body weight loss, while ifenprodil suppressed the motor and emotional withdrawal signs. Furthermore, the decrease in the food intake during withdrawal (anorexia) was significantly reduced by dizocilpine, but not by ifenprodil. These behavioral results indicated that the activation of NMDA receptors during withdrawal may play an important role in the appearance of withdrawal signs (in particular motor withdrawal signs) caused by discontinuation of chronic diazepam treatment, and that inhibitory agents for NMDA receptors may be effective in alleviation of the appearance of benzodiazepine withdrawal signs.     

Cyclic variation in stuttering: Comment on Taylor and Taylor's "Test of predictions from the conflict hypothesis of stuttering."

Although stuttering behavior may show some constancy over short time sequences as I. K. Taylor and M. M. Taylor (see 42:1) have shown, larger time segments do show a cyclic variation. Brief readings of experimental passages do not always encompass the range of cyclic occurrence. Data from B. Quarrington (see 39:5) and from the author are cited in support of the approach-avoidance conflict theory of stuttering, particularly the fear-reduction hypothesis, i.e., that the occurrence of stuttering behavior reduces the fear that elicited it. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Asymmetric neural control systems in human self-regulation.

Reviews the literature on the neurotransmitter substrates controlling motor readiness, showing that these substrates produce qualitative changes in the flow of information in the brain: Dopaminergic activation increases informational redundancy, whereas noradrenergic arousal facilitates orienting to novelty. Evidence that these neurotransmitter pathways are lateralized in the human brain is consistent with the left hemisphere's specialization for complex motor operations and the right hemisphere's integration of bilateral perceptual input. Principles of attentional control are suggested by the operational characteristics of neural control systems. The affective features of the activation and arousal systems are integral to their adaptive roles and may suggest how specific emotional processes dynamically regulate cognitive function. (4? p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A PET study on cortical and subcortical control of pelvic floor musculature in women

The possibility of hepatitis B virus (HBV) infection in HBsAg-negative patients has been shown. However, an "inapparent" coinfection by HBV in hepatitis C virus (HCV)-positive patients generally is not taken into account in clinical practice. Mechanisms responsible for resistance to interferon (IFN) have not been completely clarified. The aim of this study was to investigate whether an "inapparent" coinfection by HBV in anti-HCV-positive chronic liver disease patients may influence IFN response. Fourteen anti-HCV positive, HBsAg-negative but serum HBV DNA-positive patients by PCR and 111 anti-HCV-positive, HBsAg-negative and HBV DNA (PCR)-negative patients with chronic hepatitis were treated with 3 MU of recombinant alpha-2a IFN 3 times weekly for 12 months. Serum HBV DNA and HCV RNA were determined before treatment, after 6-12 months and in coincidence with ALT flare-up by PCR. HBV PCR was performed using primers specific for the S region of the HBV genome and HCV PCR with primers localised in the 5'NC region of HCV genome. IgM anti-HBc was tested using IMx Core-M Abbott assay. By the end of treatment, ALT values had become normal in 4/14 HBV DNA-positive patients (28%), but all "responders" (4/4) relapsed between 2 and 5 months after therapy. All but one patient were HCV RNA-positive before treatment, 6 were also both HBV DNA and HCV RNA-positive during ALT flare-ups. In 5 patients, only HBV DNA and in 3 patients, only HCV RNA was detected when transaminase values increased. All patients remained HBsAg-negative and anti-HCV-positive. IgM anti-HBc was detected both before treatment and during ALT elevation in 3 patients and only during ALT relapse in 3 others. Of the 111 anti-HCV positive, HBsAg-negative and HBV DNA (PCR)-negative patients with chronic hepatitis, a biochemical response to IFN treatment was observed in 54% of the cases. Relapse of ALT values was observed in 47% of the cases during a follow-up of 1 year after treatment. "Inapparent" HBV/HCV coinfection may be implicated in cases of resistance to IFN treatment. In addition, HBV replication may persist in patients in whom HCV replication was inhibited by IFN treatment. The pathogenic role of HBV in liver disease was confirmed by detection of IgM anti-HBc in some cases; the appearance of these antibodies only after IFN treatment suggests that IFN may exert a selective role in favour of HBV. Further studies will show the effect of different treatment schedules. HBV DNA and/or IgM anti-HBc detection with very sensitive methods may be important both as a prognostic factor and as a tool for better understanding interviral relationships and mechanisms involved in multiple hepatitis virus infections.     

A chemo-enzymatic approach to the study of carbohydrate recognition in biological systems

This report describes our recent work on the study of carbohydrate-mediated cell adhesion, including the development of new methods for carbohydrate synthesis, the inhibition of enzymes involved in the cell adhesion process and the design and synthesis of carbohydrate mimetics.     

Neural mechanisms of global and local processing. A combined PET and ERP study

The neural mechanisms of hierarchical stimulus processing were investigated using a combined event-related potentials (ERPs) and positron emission tomography (PET) approach. Healthy subjects were tested under two conditions that involved selective or divided attention between local and global levels of hierarchical letter stimuli in order to determine whether and where hemispheric differences might exist in the processing of local versus global information. When attention was divided between global and local levels, the N2 component of the ERPs (260- to 360-msec latency) elicited by the target stimuli showed asymmetries in amplitude over the two hemispheres. The N2 to local targets was larger over the left hemisphere, but the N2 to global targets tended to be slightly larger over the right hemisphere. However, the shorter-latency, sensory-evoked P1 component (90- to 150-msec latency) was not different for global versus local targets under conditions of divided attention. In contrast, during selective attention to either global or local targets, asymmetries in the N2 component were not observed. But under selective attention conditions, the sensory-evoked P1 components in the extrastriate cortex were enlarged for global versus local attention. Increased regional cerebral blood flow in the posterior fusiform gyrus bilaterally was observed in the PET data during selective attention to either global or local targets, but neither these nor the P1 component showed any tendency toward hemispheric difference for global versus local attention. Neither were there any activations observed in the parietal lobe during selective attention to global versus local targets. Together these data indicate that early sensory inputs are not modulated to gate global versus local information differentially into the two hemispheres. Rather, later stages of processing that may be asymmetrically organized in the left and right hemispheres operate in parallel to process global and local aspects of complex stimuli (i.e., the N2 effect of the ERPs). This pattern of results supports models proposing that spatial frequency analysis is only asymmetric at higher stages of perceptual processing and not at the earliest stages of visual cortical analysis.