Oral perception of liquid volume changes with age.

Bolus volume has been widely studied, and research has demonstrated a variety of physiological impacts on swallowing and swallowing disorders. Oral perception of bolus volume has not, to our knowledge, been investigated in association with normal ageing processes. Research suggests many sensory changes with age, some within the oral cavity, and changes in swallowing function with age have been defined. The role of perception in oropharyngeal deglutition with age requires further investigation. The purpose of this study was to establish the psychophysical relationship between liquid volume and oral perception and examine changes with age. Healthy young and older adults were prospectively assessed using a magnitude estimation task differentiating five volumes of water delivered randomly to the oral cavity. Results suggest a fourfold increase in liquid volume is required by older participants to perceive an approximate twofold increase in the perception of volume compared with younger healthy adults. Sensory receptors in the oral cavity provide a feedback loop that modulates the swallowing motor response so that it is optimal for the size and consistency of the bolus. Changes in perception of bolus volume with age are consistent with other perceptual changes and may provide valuable information regarding sensorineural rehabilitation strategies in the future.

Change in EEG Activity is Associated with a Decrease in Tinnitus Awareness after rTMS.

OBJECTIVE: To examine how 1Hz and 10Hz rTMS temporarily influence ratings of tinnitus loudness, annoyance, and awareness. The thalamocortical dysrhythmia (TCD) model of tinnitus was tested by examining changes in spectral power and coherence of resting state EEGs from baseline to each phase of treatment and correlating these data with change in tinnitus. METHODS: Nineteen participants completed a double-blind, placebo (sham rTMS) controlled, within-subjects study with crossover between the two active rTMS treatment conditions. An imposed order effect, sham rTMS first, eliminated drift of active treatment into the placebo condition. The primary outcome measures were analogue ratings of tinnitus loudness, annoyance, and awareness, assessed repeatedly at baseline and during treatment, and 64 channel, resting state EEGs collected at baseline and the end of each treatment phase. Active rTMS consisted of 1800 pulses at 110% of motor threshold over temporal cortex delivered at 1Hz and 10Hz over four days. The research design also examined the effect of rTMS immediately following stimulation, regression to the mean in tinnitus ratings made over multiple days, and differences between treatment responders and non-responders. RESULTS: There was no immediate effect of rTMS on tinnitus during a single rTMS session. Regression to the mean in tinnitus ratings occurred over three days of baseline and four days of treatment (both sham and active rTMS). After accounting for regression to the mean in the statistical model, 1Hz rTMS led to a significant decrease in tinnitus awareness from baseline and 10Hz rTMS trended in the same direction, whereas sham rTMS showed little change from baseline other than regression to the mean. Changes from baseline in spectral power of the resting state EEG provided partial support for predictions based on TCD model of tinnitus for active 1 and 10Hz rTMS but not sham rTMS. However, only an increase in beta coherence correlated significantly with a decrease in tinnitus awareness. Changes in the EEG were robust in treatment responders but absent among non-responders and during sham rTMS. CONCLUSIONS: A positive response to rTMS for tinnitus is associated with an rTMS-induced change in beta coherence of the EEG. Increased beta coherence may be a biomarker of the rTMS effect; a "top-down" modulation of the EEG that promotes habituation to tinnitus. Participants whose tinnitus did not improve after rTMS did not show any changes in the EEG.

Neural activity during attentional conflict predicts reduction in tinnitus perception following rTMS.

BACKGROUND: Subjective idiopathic tinnitus is an intrusive, distracting, and potentially disabling disorder characterized by phantom perception of sounds. Although tinnitus has no approved pharmacologic treatment, recent evidence supports the use of repetitive transcranial magnetic stimulation (rTMS) to alleviate tinnitus symptoms. OBJECTIVE/HYPOTHESIS: Repetitive TMS delivered over the middle superior temporal gyrus (STG) may alter ratings of tinnitus awareness and annoyance more than loudness due to change in attentional processing. STG has reciprocal connections to regions of the prefrontal cortex that mediate attention. To probe the hypothesized influence of STG stimulation on attention, a subset of patients with tinnitus enrolled in an rTMS clinical trial [n = 12, 9 male, mean (sd) age = 49 (15) years] underwent an attentional conflict task before and after rTMS treatment in a repeated-measures functional magnetic resonance imaging (fMRI) study. METHODS: The Multi-Source Interference Task (MSIT), a Stroop-based visual attentional conflict fMRI task, was used to map participants' neural processing of attentional conflict prior to rTMS intervention (Baseline) and after three rTMS intervention arms: Sham, 1 Hz, and 10 Hz (four sessions per arm, 1800 pulses per session, delivered @110% of the motor threshold over the posterior superior temporal gyrus). RESULTS: All measures of tinnitus severity (awareness, loudness, and annoyance) improved with 1 Hz rTMS intervention; however, the greatest and most robust changes were observed for ratings of tinnitus awareness (mean 16% reduction in severity from Baseline, p < 0.01). The MSIT elicited a similar pattern of neural activation among tinnitus participants at Baseline compared to an independent sample of 43 healthy comparison adults (r = 0.801, p = 0.001). Linear regression with bootstrap resampling showed that greater recruitment of bilateral prefrontal and bilateral parietal regions by MSIT at Baseline corresponded with poorer treatment response. Individual regions' activities explained 37-67% variance in participant treatment response, with left dorsolateral prefrontal cortex's MSIT activity at Baseline explaining the greatest reduction in tinnitus awareness following 1 Hz stimulation. Although left dorsolateral prefrontal cortex activity at Baseline also predicted reduction in tinnitus loudness and annoyance (∼50% variance explained), these symptoms were more strongly predicted by right middle occipital cortex (∼70% variance explained) - suggesting that the neural predictors of symptom-specific treatment outcomes may be dissociable. CONCLUSION: These candidate neural reactivity markers of treatment response have potential clinical value in identifying tinnitus sufferers who would or would not therapeutically benefit from rTMS intervention.

Contributions of the left intralaminar and medial thalamic nuclei to memory. Comparisons and report of a case.

A patient complained of memory disturbance after a small left thalamic infarction. Neuropsychological testing revealed her memory to be normal provided that she was allowed to rehearse or use semantic encoding strategies. When these strategies were prevented, her performance was impaired. Mapping of the lesion demonstrated involvement of the caudal intralaminar nuclei (centre médian and parafascicular nuclei), and portions of the medial nuclei (medioventral [reuniens], centromedial, and the most inferior aspect of the mediodorsal nucleus). The majority of mediodorsal nucleus, the mammillary bodies, the mammillothalamic tract, and the anterior thalamic nuclei, were spared. A comparison among our patient's performances and those of alcoholic Korsakoff patients, patient NA, and amnestic patients with circumscribed diencephalic lesions suggests that there are two distinct behavioral and anatomic types of memory impairment associated with diencephalic lesions. The severe amnesia associated with damage to the mammillary bodies, midline nuclei, mammillothalamic tract, and/or dorsomedial nucleus of the thalamus (eg, Korsakoff and NA) is characterized by encoding deficits that never approximate normal performance. The memory disturbance associated with damage to the intralaminar and medial nuclei of the thalamus is milder and is characterized by severe distractibility.

Variability not ability: another basis for performance decrements in neglect.

OBJECTIVE: To determine reaction time (RT) and its variability, as a function of horizontal spatial position, in subjects with neglect. BACKGROUND: In neglect, performance is frequently reported a as mean and a decreased ability to perform the task inferred by comparison to control groups. Few studies have examined how consistency and optimal performance relate to spatial neglect. METHODS: Ten subjects with brain damage, five with and five without spatial neglect, were assessed on a RT task. Subjects responded by pushing a computer key to the onset of a white square appearing on a black screen. The locations of stimuli were randomly varied along the horizontal meridian. RESULTS: For three of five neglect subjects, optimal RT showed no or little relation to horizontal location. Four of five neglect subjects demonstrated an increased variability in RT that correlated with spatial position and which was not present in our brain damaged subjects without neglect. The relationship was not an artifact of left sided stimuli, in general, being processed differently. For the two neglect subjects with the most trials, a significant correlation between RT variability and spatial position existed for left-sided trials alone. Increased variability was not a consequence of simply looking left proportionately less often, nor could a model of multiple compensatory systems operating in parallel explain the enhanced variability. Neither hemianopsia alone nor brain damage per se could account for the spatial modulation of RT variability. CONCLUSIONS: That neglect subjects perform the RT task normally on some trials, even in their 'neglected field', challenges the notion that neglect must reflect an irreparably damaged cognitive system. Performance decrements in neglect can reflect an inability to consistently detect and respond. Evaluating optimal performance and variability of performance can indicate if a capacity has been lost absolutely or merely degraded such that normal performance cannot be sustained.

Search patterns and neglect: a case study.

An irregular and unsystematic search pattern may contribute to unilateral neglect. We examined the sequence of cancellations performed by a patient with unilateral neglect and found that she followed a systematic and stereotypic vertical search pattern. To overcome this vertical search pattern, foils were placed in rows. These foils induced slightly more horizontal movements, but did not alter her neglect. In another attempt to overcome her vertical search and tendency to cancel on the right, she was explicitly instructed to cancel targets alternating to and from the right and left sides of the array. This strategy overcame her vertical search, but, instead of modifying the severity of her neglect, this task only changed its spatial distribution. The altered spatial distribution of neglect is difficult to reconcile with current theories of neglect. We suggest that this patient demonstrates a limited capacity to sequentially be aware of or act upon stimuli.

A stimulus-response relationship in unilateral neglect: the power function.

We have previously suggested that patients with unilateral neglect may be limited in their ability to sequentially attend or act upon stimuli. To assess the nature of this capacity limitation, we examined the relationship between number of stimuli presented on cancellation arrays and how many targets a patient with neglect cancelled. This relationship was systematic and described by a power function: targets cancelled = K (targets presented)B, in which the constant and exponent were derived empirically. Density of targets and time taken to cancel targets did not account for the relationship. Improvement on subsequent testing was reflected in an increase in the constant. However, the exponent of the power function did not change, suggesting that some critical aspect of her dysfunction remained the same. These data also imply that she had implicit knowledge of quantity of stimuli presented, and that this knowledge systematically influenced her explicit behavior.

Contributions of the parietal and frontal lobes to sustained attention and habituation.

The parietal cortex may be important in sustaining attention toward visual stimuli in peripheral space whereas the frontal cortex may mediate selective attention through habituation to peripheral stimuli. To test this hypothesis, patients with focal lesions of either the parietal or frontal cortex or both and normal controls were studied using a paradigm known as Troxler fading. Accordingly, if one fixates on a centrally located stimulus and attends to a stationary stimulus in peripheral vision, the peripheral stimulus quickly fades from awareness (i.e. Troxler fading: Troxler [Verschwinden, unseres, Opthal, Vol. 2, pp. 51-53. Fromann, Jena, 1804]). Movement of the peripheral stimulus on the retina normally prevents Troxler fading. Results indicated that patients with parietal lesions not only reported accelerated Troxler fading but also reported fading of moving peripheral stimuli contralateral to their brain lesion. In contrast, patients with frontal lesions rarely reported Troxler fading. In one patient with a left parietal and a right frontal lobe lesion fading was hemi-spatially dissociated, being accelerated in right hemispace but absent in left hemispace. These observations suggest that the parietal and frontal cortices play complementary roles in attentional processing.

Contributions of the left and right cerebral hemispheres to line bisection.

Thirty-one right-hemisphere lesioned (RHL) patients, 11 left-hemisphere lesioned patients (LHL) and 10 normal controls (NC) bisected lines in three spatial location and four directional cuing conditions. The error direction and error size were analyzed as separate and combined variables. Seventy-seven percent of RHL patients and 45% of LHL patients made abnormally large errors in line bisection. Right-hemisphere lesioned patients were more sensitive to spatial location and directional cuing than NC subjects. In contrast, LHL patients were less sensitive to either condition than NCs. The error direction and error size emerged as dissociable components of line bisection. Right-hemisphere lesioned patients and NC subjects bisected lines consistently to one side of the true center. Left-hemisphere lesioned patients bisected lines equally often on both sides of the true center. Both RHL and LHL patients made larger absolute bisection errors than NC subjects, but the RHL patient's errors were larger than those of the LHL patients. We propose that the greater sensitivity of RHL patients to spatial location and directional cues and the directional consistency of their bisection errors represent contributions of the intact left cerebral hemisphere to line bisection. In contrast, the LHL patient's unrestrained ability to orient to both ends of the line reflects a contribution of the intact right cerebral hemisphere to line bisection. The failure of both groups to accurately bisect lines reflects a common visuospatial processing deficit that is more pronounced following RHLs than LHLs.

Tapping, talking and the thalamus: possible influence of the intralaminar nuclei on basal ganglia function.

A patient with a discrete lesion of the left, intralaminar thalamic, nuclei exhibited a paradoxical finding with regard to finger-tapping. Normal subjects typically reduce their tapping rate when performing simultaneous verbal activity. Tapping was impaired in our patient's contralesional hand on baseline trials; however, performing the controlled oral word association (COWA) task, while finger-tapping, normalized her deficit. Subsequent experiments showed that motoric tasks rather than cognitive aspects of the COWA task were critical in potentiating finger-tapping performance. A SPECT study performed at rest revealed focal perfusion asymmetries in motor and premotor cortices. Because the caudal intralaminar nuclei project heavily to the striatum, striatal deafferentiation may account for these asymmetries. These observations provide some insight into the influences of the caudal intralaminar thalamic nuclei on basal ganglia function and the basal ganglia's influence on motor gating.

Thalamic thought disorder: on being "a bit addled".

Humans can generate and maintain relatively coherent trains of thought in natural discourse. The neural mediation of this ability and the phenomenology of its breakdown are not well understood. We report a case of a woman with paramedian thalamic strokes involving the mammillothalamic tract, intralaminar nuclei, parts of the dorsomedial and ventral lateral nuclei bilaterally. She presented with a dense amnesia and confusion typical of the syndrome of bilateral paramedian thalamic infarcts. Her Tc-99m HMPAO brain SPECT scan showed decreased thalamic and basal ganglia blood flow. General diminution of cerebral blood flow and areas of further diminution in the right frontal, left temporal and left temporoparietal regions were also observed. Although her amnesia was characteristic of diencephalic amnesia, her most striking clinical feature was a bizarre, disconnected and at times incoherent speech output. Analysis of her speech revealed relatively preserved lexical and morpho-syntactic linguistic production. By contrast, analysis of the macrostructure of her discourse revealed frequent unpredictable topic shifts that were completely unconstrained by contextual factors. Many of her shifts were intrusions from previous topics. We interpret her severely disordered speech output as representing the surface manifestations of a thought disorder (rather than as a language disorder per se) characterized by an inability to maintain and appropriately shift themes that normally guide discourse. Median and intralaminar thalamic nuclei appear to be critical for the neurophysiologic regulation of thalamocortical and striatocortical circuits, which in turn may be critical for the functional regulation of contextually appropriate transitions of thought.

Teaching social/vocational skills to retarded adults with a modified table game: an analysis of generalization.

In this study, a social skills training program for institutionalized mildly or moderately retarded adults was extended to include skills relevant to vocational settings. Target behaviors involving a verbal action or reaction within six skill areas were taught using a commercially available board game, Sorry, and a specially designed card deck. The training program featured response specific feedback, self-monitoring, individualized reinforcers, and individualized performance criterion levels. Using a multiple baseline across two groups (n = 3 per group), the game contingencies increased social/vocational skills in all targeted areas. Generalization was assessed in two settings: a simulated workshop in which pre and post measures were taken and in the institutional workshop where the residents worked. The posttraining simulated workshop results revealed that the residents' newly learned skills had generalized. However, repeated generalization measures of the residents' social interactions in the institutional workshop were equivocal as were measures of their productivity.

Laterality, frequency and replication of rTMS treatment for chronic tinnitus: pilot studies and a review of maintenance treatment.

This manuscript reports on findings of three open-label, pilot studies and it reviews studies using rTMS as a maintenance treatment for any disorder. The first pilot study examined whether a patient's original treatment response to 1 Hz rTMS over temporal cortex could be replicated by stimulating a homologous region of the opposite hemisphere. The second study examined whether a patient's response to 1 Hz rTMS could be replicated by applying 10 Hz rTMS over the same treatment site. The third study applied a 3-day course of maintenance rTMS, either at 1 or 10 Hz, when subjects indicated that the benefit of their last course of treatment was waning. Patients with bilateral subjective tinnitus of at least 6 months duration were recruited from a prior, sham controlled study with treatment crossover that applied 1 Hz rTMS over temporal cortex. Both treatment responders and non-responders were recruited. Results indicated, first, that the original treatment response, both positive and negative, is replicated after stimulating a homologous region of the opposite hemisphere; second, patients respond similarly to 1 and 10 Hz stimulation of the same treatment site (an exception was one patient who initially failed 1 Hz stimulation but responded positively to 10 Hz stimulation); and, third, maintenance rTMS had a sustained and additive benefit for tinnitus among treatment responders. Conclusions are that rTMS-induced effects on tinnitus are neither hemisphere specific nor frequency dependent; although, different frequencies of rTMS may have greater potency for a given subject. Maintenance treatment is a well tolerated approach with demonstrated feasibility for managing chronic tinnitus in persons who respond positively to an initial course of treatment.

Sham Transcranial Magnetic Stimulation Using Electrical Stimulation of the Scalp.

BACKGROUND: Most methods of sham, repetitive transcranial magnetic stimulation (rTMS) fail to replicate the look, sound, and feel of active stimulation in the absence of a significant magnetic field. OBJECTIVE/HYPOTHESIS: To develop and validate a new method of sham rTMS appropriate for a double-blind, placebo-controlled study with subject crossover. METHODS: The look and sound of active rTMS was replicated using a matched, air-cooled sham TMS coil. Scalp muscle stimulation associated with rTMS was replicated using large rubber electrodes placed over selected muscles. The intensity and pulse width of electrical stimulation necessary to match 1-Hz rTMS was developed in one sample of normal subjects. The sham technique was validated in back-to-back comparisons with active rTMS in new samples of normal subjects who were either naïve or experienced with rTMS. RESULTS: Subjects naïve to TMS could not tell which type of stimulation was active or sham or which was electrical or magnetic. Naïve subjects incorrectly picked sham stimulation as active, when forced to choose, because electrical stimulation felt more focused than magnetic stimulation. Subjects experienced with TMS could correctly identify sham and active stimulation. Experimenters could detect subtle differences between conditions. CONCLUSIONS: This method of sham rTMS closely mimics the look, sound, and feel of active stimulation at 1Hz without creating a significant magnetic field. It is valid for use with naïve subjects and in crossover studies. It can accommodate differences in scalp muscle recruitment at different sites of stimulation, and it could potentially be used with higher frequency stimulation.

Perception of motor strength and stimulus magnitude are correlated in stroke patients.

The authors examined whether perception of contralateral limb strength is altered and whether perception of strength correlates with perception of stimulus intensity (magnitude) in a prospective sample of patients with unilateral right (RHL: n = 13) and left (LHL: n = 6) hemisphere lesions due to stroke. Patients with RHL tended to overestimate strength and patients with LHL tended to underestimate strength; both patterns were highly correlated with altered perception of stimulus magnitude.

The psychophysical power law and unilateral spatial neglect.

The relationship between objective measures and subjective experiences of sensory stimuli is described by a power law, psi = K phi beta, in which psi represents the psychological value and phi the physical value. The constant (K) and the exponent (beta) are empirically derived. This relationship is often assumed to correspond to properties of peripheral receptor sensory transduction. Patients with left-sided spatial neglect tend to bisect lines to the right of the objective midline. Line bisection bias was used as the dependent variable in how a patient with neglect and five normal subjects bisected lines of varying lengths. Analyzing these data as a power function accounted for over 99% of the variance in five different experimental conditions. The normal exponent matched the value expected from traditional psychophysical experiments of line length estimation, whereas the patient's exponent was diminished. The patient's data provide evidence for central nervous system participation in computations underlying psychophysical relationships. The notion that attentional and perceptual processes are closely linked was supported by the influence of attentional cuing on the power functions obtained in normal subjects. The descriptive precision of the power function uncovered qualitative variability in how normal subjects allocate attention across different spatial reference frames and demonstrated that this patient had a quantitative defect in directing attention across an allosteric reference frame, but a qualitative defect in directing attention across a viewer/environment reference frame.

Neglect of near peripersonal space. Evidence for multidirectional attentional systems in humans.

Neglect is most commonly observed and studied in the horizontal spatial dimension. Vertical neglect has been described in a few studies. We now report on a patient with near radial space neglect following bilateral posterior parietal lobe lesions. Our patient also had neglect of inferior vertical and left horizontal space. These spatial deficits appear primarily attentional. Our findings compliment other studies that demonstrate neglect may occur in multiple spatial dimensions and provide evidence for a three-dimensional attentional system in humans. Whereas neglect of inferior vertical space may be associated with bilateral parietal lobe lesions, neglect of superior vertical and far radial space has been associated with bilateral inferior temporo-occipital lesions.

Memory, mood and measurement in hypothyroidism.

A 63-year-old female exhibited primary hypothyroidism, both upon clinical examination and laboratory tests. A full neuropsychological exam and repeated, multiple measures of affect, memory, concentration, and problem solving were used to establish baselines prior to treatment and to assess change during the first 7 months of thyroid hormone replacement therapy. Additionally, thyroid hormone and metabolites T3, T4, TSH, and T3 (resin uptake) were regularly assessed. Results indicated that establishing stable baselines before treatment, long-term repeated assessments during treatment, and the use of control subjects are crucial to understanding the neuropsychological changes associated with hypothyroidism. Certain measures of depression, anxiety, attention, and concentration changed from severely impaired to normal levels following an explanation of the diagnosis but before actual treatment. Baseline memory functions were impaired before treatment and remained impaired relative to normals during replacement therapy in spite of improvement with repeated testing. However, replacement therapy may have arrested the progression of memory deterioration as no further decline was evident at a 7-month follow-up. Our data suggest that the memory changes associated with primary hypothyroidism may not be reversed by thyroid hormone replacement therapy.

A comparison of the influences of body and environment centred reference frames on neglect.

Extrapersonal space can be defined by coordinate systems, or frames of reference, that are centred on the body (viewer) or on the environment. Although these frames are identical in the upright position, when the body is placed in positions orthogonal to gravity, the frames may be dissociable. We compared the influences of environmental and body-centred frames on line bisection in two patients with neglect who, when upright, neglected opposite dimensions of space. Through certain combinations of line placement and body orientation, the body and environmental frames were brought into opposition, and each frame predicted line bisection errors in an opposite direction. When the patients were positioned so that predictions of the two frames contrasted, both bisected lines as predicted by the environmental rather than the body-centred frame.