Bilateral parietal contributions to spatial language.

It is commonly held that language is largely lateralized to the left hemisphere in most individuals, whereas spatial processing is associated with right hemisphere regions. In recent years, a number of neuroimaging studies have yielded conflicting results regarding the role of language and spatial processing areas in processing language about space (e.g., Carpenter, Just, Keller, Eddy, & Thulborn, 1999; Damasio et al., 2001). In the present study, we used sparse scanning event-related functional magnetic resonance imaging (fMRI) to investigate the neural correlates of spatial language, that is; language used to communicate the spatial relationship of one object to another. During scanning, participants listened to sentences about object relationships that were either spatial or non-spatial in nature (color or size relationships). Sentences describing spatial relationships elicited more activation in the superior parietal lobule and precuneus bilaterally in comparison to sentences describing size or color relationships. Activation of the precuneus suggests that spatial sentences elicit spatial-mental imagery, while the activation of the SPL suggests sentences containing spatial language involve integration of two distinct sets of information - linguistic and spatial.

Neuronal injury in the motor cortex after chronic stroke and lower limb motor impairment: a voxel-based lesion symptom mapping study.

Many studies have examined motor impairments using voxel-based lesion symptom mapping, but few are reported regarding the corresponding relationship between cerebral cortex injury and lower limb motor impairment analyzed using this technique. This study correlated neuronal injury in the cerebral cortex of 16 patients with chronic stroke based on a voxel-based lesion symptom mapping analysis. Neuronal injury in the corona radiata, caudate nucleus and putamen of patients with chronic stroke could predict walking speed. The behavioral measure scores were consistent with motor deficits expected after damage to the cortical motor system due to stroke. These findings suggest that voxel-based lesion symptom mapping may provide a more accurate prognosis of motor recovery from chronic stroke according to neuronal injury in cerebral motor cortex.

The effect of stimulus duration and motor response in hemispatial neglect during a visual search task.

Patients with hemispatial neglect exhibit a myriad of profound deficits. A hallmark of this syndrome is the patients' absence of awareness of items located in their contralesional space. Many studies, however, have demonstrated that neglect patients exhibit some level of processing of these neglected items. It has been suggested that unconscious processing of neglected information may manifest as a fast denial. This theory of fast denial proposes that neglected stimuli are detected in the same way as non-neglected stimuli, but without overt awareness. We evaluated the fast denial theory by conducting two separate visual search task experiments, each differing by the duration of stimulus presentation. Specifically, in Experiment 1 each stimulus remained in the participants' visual field until a response was made. In Experiment 2 each stimulus was presented for only a brief duration. We further evaluated the fast denial theory by comparing verbal to motor task responses in each experiment. Overall, our results from both experiments and tasks showed no evidence for the presence of implicit knowledge of neglected stimuli. Instead, patients with neglect responded the same when they neglected stimuli as when they correctly reported stimulus absence. These findings thus cast doubt on the concept of the fast denial theory and its consequent implications for non-conscious processing. Importantly, our study demonstrated that the only behavior affected was during conscious detection of ipsilesional stimuli. Specifically, patients were slower to detect stimuli in Experiment 1 compared to Experiment 2, suggesting a duration effect occurred during conscious processing of information. Additionally, reaction time and accuracy were similar when reporting verbally versus motorically. These results provide new insights into the perceptual deficits associated with neglect and further support other work that falsifies the fast denial account of non-conscious processing in hemispatial visual neglect.

Conditioning of transcranial magnetic stimulation: evidence of sensory-induced responding and prepulse inhibition.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a non-invasive method for stimulating the human cortex. Classical conditioning is a phenomenon of developed associations between stimuli. Our primary objective was to determine whether TMS effects could be conditioned. Prepulse inhibition represents another relationship between two stimuli, and a secondary assessment was performed to explore this relationship. METHODS: An auditory-visual conditioning stimulus (CS) was paired with the TMS unconditioned stimulus (US) over motor cortex producing a motor-evoked potential (MEP) unconditioned response (UR). Two versions of the CS-US pairing paradigms were tested, one with a short intertrial interval (ITI) and another with a long ITI. The short ITI paradigm had more CS-US pairings and shorter session duration than the long ITI paradigm. Tests for conditioned responses (CRs) were performed following CS-US pairing (CS+/US+), by presenting the CS alone (CS+/US-). Reverse testing was also performed after CS-US pairing (CS+/US+) in separate sessions, by presenting the US alone (CS-/US+). RESULTS: Evidence for CRs was found only with the short ITI paradigm. The magnitudes of CRs were smaller than TMS-induced MEPs, and the CRs were found only in a percentage of tests. Prepulse inhibition was robustly evident for the long ITI paradigm, but not for the short ITI paradigm. CONCLUSIONS: We have found evidence that classical conditioning principles can be applied to brain stimulation in humans. These findings provide a method for exploring brain and behavioral relationships in humans, as well as suggesting approaches to enhance therapeutic uses of TMS or other forms of brain stimulation.

Visual extinction: the effect of temporal and spatial bias.

Unlike patients with neglect, neurological patients with extinction can detect a single event presented at any location. However, when shown two brief near-simultaneous stimuli they only report the ipsilesional item. The question of what inter-stimulus delay leads to maximal extinction has clear clinical and theoretical implications. di Pellegrino et al. [di Pellegrino, G., Basso, G., & Frassinetti, F. (1997). Spatial extinction on double asynchronous stimulation. Neuropsychologia, 35, 1215-1223] report that extinction is maximal when the two stimuli are presented simultaneously, with less extinction when either item has a slight temporal lead. This finding supports traditional clinical diagnosis (which only presents simultaneous events), and is in accord with theories of extinction that entail individuation of objects (e.g. "token" accounts). In contrast, Cate and Behrmann [Cate, A., & Behrmann, M. (2002). Spatial and temporal influences of extinction. Neuropsychologia, 40, 2206-2225] report that extinction is maximal when the ipsilesional item is presented slightly prior to the contralesional item. This finding appears to support disengage models of attention. Our aim was to reveal whether the difference between these studies reflects different patients, or different methods. Specifically, we note that the stimuli used by Cate and Behrmann were biased both temporally (more ipsilesional first trials) and spatially (more items presented in ipsilesional field). We examined the performance of nine individuals with extinction, and found that maximal extinction was not influenced by temporal biases, but extinction was modulated by the spatial location of stimuli. This finding reconciles previous studies and offers new insight into this syndrome.

Event related potentials reveal that increasing perceptual load leads to increased responses for target stimuli and decreased responses for irrelevant stimuli.

Lavie (1995) have suggested that perceptual processing is influenced by perceptual load. Specifically, relevant information receives additional processing in high load situations exhausting the available capacity. On the other hand, irrelevant information receives less processing with increasing load on a relevant task, as there is a reduced amount of residual processing available. Rees et al. (1997) provided the first physiological evidence for this model, showing this pattern in a functional magnetic resonance imaging study. Likewise, Handy et al. (2001) offered supporting evidence measuring event related potentials (ERPs). Both of these studies presented irrelevant information in peripheral vision. Here we manipulated load while using the identical stimuli and the same task (a peripheral gap judgment task) with centrally presented irrelevant stimuli. ERPs show the pattern predicted by Lavie and colleagues, specifically for the N1 component. This work offers further evidence that visual attention modulates relatively early processing of perceptual information. Specifically, increasing load resulted in stronger N1 responses to relevant information and weaker N1 responses to irrelevant information.

Motor speech perception modulates the cortical language areas.

Traditionally, the left frontal and parietal lobes have been associated with language production while regions in the temporal lobe are seen as crucial for language comprehension. However, recent evidence suggests that the classical language areas constitute an integrated network where each area plays a crucial role both in speech production and perception. We used functional MRI to examine whether observing speech motor movements (without auditory speech) relative to non-speech motor movements preferentially activates the cortical speech areas. Furthermore, we tested whether the activation in these regions was modulated by task difficulty. This dissociates between areas that are actively involved with speech perception from regions that show an obligatory activation in response to speech movements (e.g. areas that automatically activate in preparation for a motoric response). Specifically, we hypothesized that regions involved with decoding oral speech would show increasing activation with increasing difficulty. We found that speech movements preferentially activate the frontal and temporal language areas. In contrast, non-speech movements preferentially activate the parietal region. Degraded speech stimuli increased both frontal and parietal lobe activity but did not differentially excite the temporal region. These findings suggest that the frontal language area plays a role in visual speech perception and highlight the differential roles of the classical speech and language areas in processing others' motor speech movements.

Activation of brain attention systems in individuals with symptoms of ADHD.

Previous research investigating attention and impulse control in individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) has largely ignored the symptomatic differences among the three subtypes of ADHD: ADHD-Inattentive Type, ADHD-Hyperactive/Impulsive Type, and ADHD-Combined Type. The present study examined attention and impulse control by focusing on these subtypes. Based on their self-reported symptoms of ADHD, participants belonged to one of four groups: ADHD-Inattentive, ADHD-Hyperactive/Impulsive, ADHD-Combined, and control. Cortical activity was recorded from participants during performance of a Go/NoGo task. The event-related potentials (ERP) measured at frontal and posterior sites discriminated between the control group and participants with symptoms of ADHD. The control group consistently exhibited a higher P3 amplitude than all the ADHD groups. The main difference occurred at the frontal site, indicating that individuals with ADHD symptoms have deficits in the anterior attentional system, which mediates signal detection. Behavioral measures of signal sensitivity revealed that the ADHD-Inattentive and the ADHD-Hyperactive/Impulsive groups had more difficulty with the attention-demanding Go/NoGo respond-to-target task, while behavioral measures of response bias indicated that the ADHD-Hyperactive/Impulsive and the ADHD-Combined groups responded more liberally in the inhibition-demanding Go/NoGo suppress-to-target task.

Neural correlates of phonological and semantic-based anomia treatment in aphasia.

Most naming treatments in aphasia either assume a phonological or semantic emphasis or a combination thereof. However, it is unclear whether semantic or phonological treatments recruit the same or different cortical areas in chronic aphasia. Employing three persons with aphasia, two of whom were non-fluent, the present study compared changes in neural recruitment associated with phonologic and semantic-based naming treatments. The participants with non-fluent aphasia were able to name more items following both treatment approaches. Although this was not the case for the participant who had fluent aphasia, her naming errors decreased considerably following treatment. Post-treatment fMRI revealed similar changes in neural activity bilaterally in the precuneus among the two non-fluent participants--increased activity was noted in the right entorhinal cortex and posterior thalamus on post-treatment scans for the third participant. These findings imply that cortical areas not traditionally related to language processing may support anomia recovery in some patients with chronic aphasia.

Age-related variability in cortical activity during language processing.

PURPOSE: The present study investigated the extent of cortical activity during overt picture naming using functional magnetic resonance imaging (fMRI). METHOD: Participants comprised 20 healthy, adult participants with ages ranging from 20 to 82 years. While undergoing fMRI, participants completed a picture-naming task consisting of 60 high-frequency nouns. RESULTS: Linear regression analysis revealed a positive relationship between age and cortical activation intensity in Broca's and Wernicke's areas as well as the right-hemisphere homologue of Broca's area. In contrast, neural activity in the anterior cingulate gyrus, an area thought to be involved in attentional processing, did not increase as a function of age. CONCLUSIONS: These findings suggest age-related increases in cortical activation during simple language tasks, such as picture naming, in brain areas typically associated with language processing.

Measuring the hemodynamic response in chronic hypoperfusion.

Although structural brain scans help assess brain injury in stroke, they cannot identify regions that are functionally disabled due to disrupted perfusion. Perfusion and functional MRI have the potential for determining the functional consequences of stroke. Here we examine the effectiveness of functional MRI to measure brain function in a single patient (LB) with chronic hypoperfusion. When LB made sustained hand movements we observed a sustained decrease in the fMRI signal, while normal individuals exhibit a sustained increase in signal while conducting this task. This work has clear implications for understanding stroke using functional MRI.

Speech apraxia without oral apraxia: can normal brain function explain the physiopathology?

Apraxia of speech, usually associated with stroke, refers to the inability to perform speech motor movements typically with an intact ability to execute non-speech oral movements. It is uncertain whether apraxia of speech results from damage affecting the insula or the inferior frontal gyrus. The controversy started because of conflicting results from studies investigating patients with disrupted brain structure, when dysfunction of both sites can coexist. We conducted a functional magnetic resonance imaging study of individuals without neurological disorders comparing speech and non-speech movements. Speech movements did not recruit the insula, but activated the left inferior frontal gyrus, suggesting that Broca's area, but not the insula, is critical for speech articulation.

Brain damage and cortical compensation in foreign accent syndrome.

Foreign Accent Syndrome (FAS) is a well-known neurological deficit whose underlying cause has remained obscure despite almost a century of study. Combining structural and functional imaging, our studies suggest that FAS represents a compensatory response to impaired motor regulation of speech. We describe a patient who acquired FAS as a result of an ischemic stroke in the left basal ganglia. In addition to this case being exceptionally clean, we were able to confirm a specific lesion location as well as provide strong evidence that impaired motor speech regulation resulted in compensation by other areas of the cortical motor speech network.

Visual neglect can be object-based or scene-based depending on task representation.

Three patients with visual neglect were tested on their ability to detect target letters at ipsilesional and contralesional locations on a monitor, and at different locations within large shapes on the monitor. When patients were asked to detect targets within the entire monitor, they showed neglect for all the contralesional hemifield. In contrast when they were asked to detect targets within a particular object, they showed object-based neglect. In these two conditions the displays, the targets and the response were identical, with the only difference being the space that is represented for the task. These results show that the reference frame of visual neglect may be altered by task-instructions changing how a structured visual scene is represented, with neglect applying to the contralesional side of this represented space.

Auditory extinction: the effect of stimulus similarity and task requirements.

Auditory extinction was examined in six patients with right hemisphere lesions, using an auditory double simultaneous stimulation task using letters spoken in male and female voices. Patients had to detect where the stimuli were located, and identify either the letter or the voice (the task-relevant dimension). Auditory extinction was greatest when the two stimuli were the same on the task-relevant dimension, paralleling previous studies of visual extinction. Furthermore, we found that errors of omission were much less frequent in the contralesional field if the patients were not required to report both identity and the location of stimuli. These results are consistent with the notion that auditory extinction may be due in part to a failure to bind together identity and location.

The effect of ipsilesional cues on line-bisection errors: the importance of predictive value.

Patients with unilateral neglect were tested on a line-bisection task in which vertical lines were added to the ipsilesional or contralesional end. During some blocks, these vertical lines accurately predicted the horizontal length of the line, while on other blocks the vertical lines had little predictive value. We found that much of the improvement for ipsilesional vertical bars can be explained by their ability to predict the extent of the horizontal line. These results suggest that the predictive value of a ipsilesional cue is responsible for the reduction in line-bisection errors noted by Halligan and Marshall [Neuropsychologia 32 (1994) 13]. This effect of the predictive ipsilesional cue may work in combination with the expanded attentional effects posited by the ipsilesional contraction model that they proposed.

Visual extinction with double simultaneous stimulation: what is simultaneous?

Patients with unilateral lesions to the parietal lobe leading to extinction were tested with stimuli presented in both hemifields. In addition to simultaneous presentation of two stimuli, trials were given with the contralesional or ipsilesional side having an onset slightly before the other. In the first experiment, subjects were asked to identify the stimuli. In agreement with di Pellegrino et al. [Neuropsychologia 35(1997)1215], all patients showed maximal extinction when the stimuli were physically simultaneous. In the second experiment, the same patients were requested to report whether the left or right item had been presented first. In accordance with Rorden et al. [Neuropsychologia 35(1997)421], all three patients required the contralesional item to have a significant lead in order to in order to be judged as occurring first. Taken together, these findings appear to present a paradoxical picture of extinction: the first task implies that items compete maximally when they are physically simultaneous, while the second study suggests that the physical simultaneity is not phenomenally special to the patients. Attempts to reconcile these findings with popular models of extinction are discussed.