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Biomedical subjects

S L Small

Publications and source records attributed to S L Small.

At least 19 recordsLinked to original sources
PubMed2002

Cerebellar hemispheric activation ipsilateral to the paretic hand correlates with functional recovery after stroke.

An experimental lesion in the primary motor or sensory cortices in monkeys leads to functional reorganization in areas surrounding the lesion or in contralateral homologous regions. In humans, task-dependent brain activation after motor stroke seems to be multifocal and bilateral. Although many active structures are seen after stroke, their roles are unclear. For instance, the uninjured primary motor cortex may play a significant role in recovery or may be associated with mirror movements. Other motor areas, particularly those outside the affected middle cerebral artery distribution, have also been thought to play such a role, including the medial pre-motor areas and both cerebellar hemispheres. The lateral pre-motor areas might also contribute but the demarcation of primary motor and pre-motor cortices is not trivial. It is not known from existing studies how brain activation relates to behavioural change over the time course of recovery. We used functional MRI (fMRI) to study 12 patients longitudinally over the first 6 months of stroke recovery. All subjects had acute stroke causing unilateral arm weakness and had some ability to move the impaired hand within 1 month. Each patient had both motor testing and fMRI during finger and wrist movements at four points during the observed period. Six of these patients showed good motor recovery, whereas the other six did not. The imaging results support a role for the cerebellum in mediating functional recovery from stroke. The data suggest that patients with good recovery have clear changes in the activation of the cerebellar hemisphere opposite the injured corticospinal tract. Patients with poor recovery do not show such changes in cerebellar activation. No other brain region had a significant correlation with recovery. Interestingly, activation in the cerebellum ipsilateral to the injury increases transiently after stroke, independently of the success of recovery. The present work suggests a possible link between cerebellar activation and behavioural recovery from hand weakness from stroke. The underlying mechanism is not known, but it could relate to haemodynamic changes such as diaschisis or to the postulated role of the cerebellum in motor skill learning.

Acute Disease↗
PubMed2001

The anatomy of auditory word processing: individual variability.

This study used functional magnetic resonance imaging (fMRI) to investigate the neural substrate underlying the processing of single words, comparing activation patterns across subjects and within individuals. In a word repetition task, subjects repeated single words aloud with instructions not to move their jaws. In a control condition involving reverse speech, subjects heard a digitally reversed speech token and said aloud the word "crime." The averaged fMRI results showed activation in the left posterior temporal and inferior frontal regions and in the supplementary motor area, similar to previous PET studies. However, the individual subject data revealed variability in the location of the temporal and frontal activation. Although these results support previous imaging studies, demonstrating an averaged localization of auditory word processing in the posterior superior temporal gyrus (STG), they are more consistent with traditional neuropsychological data, which suggest both a typical posterior STG localization and substantial individual variability. By using careful head restraint and movement analysis and correction methods, the present study further demonstrates the feasibility of using overt articulation in fMRI experiments.

Adult↗
PubMed2001

Lateralization of motor circuits and handedness during finger movements.

Although functional lateralization in the human brain has been studied intensively, there remains significant controversy over the brain mechanisms that instantiate it. The main objective of the present study is to characterize the regions associated with the generation of different movements by the fingers of both hands by right- and left-handed people. Thirteen right- and left-handers were studied using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) during performance of single and sequential finger movement tasks. We used single-shot whole-brain spiral fMRI to map the functional components of the motor system during these tasks. Regions of interest included the primary motor and sensory cortices, the pre-motor cortices and the cerebellum. Sequential movements were associated with intense brain activation in several bilateral regions, whereas single movements were associated with less activation in fewer regions, but with greater laterality. Right- and left-handers differed in their pattern of activation, sharing a pattern of activation on simple movements but responding differently to sequential movements. On simple movements, the brain activation patterns of left- and right-handers were similar in volume, number of areas and laterality. By contrast, on sequential movement, left-handers activated larger volumes and a larger number of brain areas than right-handers, and showed significantly less brain lateralization. These results highlight differences in the functional organization of motor areas in right- and left-handed people. The discrepancies that might reflect differences in the network features of motor systems in these two groups, could also determine differences in motor activity that occur during recovery from injury (e.g. after stroke).

Adult↗
PubMed2001

Somatotopy in human primary motor and somatosensory hand representations revisited.

High-resolution functional magnetic resonance imaging of healthy volunteers was used to study the functional anatomy of the human primary motor (M1) and somatosensory (S1) cortical hand representations during simple movements of thumb, little finger and wrist and a sequential movement of the middle three fingers. Rest served as a control state. The results demonstrated an orderly somatotopy in both M1 and S1, even though the cortical areas active with individual movements significantly overlapped. Moreover, the activation patterns in M1 and S1 differed in three aspects: (i) S1 activation was distributed into significantly more clusters than M1 and the primary cluster was smaller; (ii) the overlaps of areas active with different movements were significantly larger in M1 than in S1; (iii) the difference between the three-finger sequential movement and the single-finger movements was more pronounced in S1 than in M1. The sequence-activated S1 cortex was distributed into significantly more clusters. There was also a trend for a bigger volume difference between sequence and the single finger movements in S1 than M1. These data suggest that while the distributed character dominates in M1 and S1, a somatotopic arrangement exists for both M1 and S1 hand representations, with the S1 somatotopy being more discrete and segregated, in contrast to the more integrated and overlapping somatotopy in M1.

Adult↗
PubMed2000

Pattern of olfactory bulb innervation returns after recovery from reversible peripheral deafferentation.

The olfactory epithelium (OE) is unusual in its ability to regenerate and reinnervate its target, the olfactory bulb (OB), after deafferentation. To address the question of whether olfactory receptor neuron (ORN) axons preserve their topographic organization when they reestablish synaptic contact with the OB, the authors examined the pattern of ORN axon reinnervation into the bulb of adult H-OMP-lacZ-6 transgenic mice during and after recovery from chemical deafferentation. In the H-OMP-lacZ-6 mouse strain, lacZ expression is limited to a subset of ORNs that are distributed bilaterally in the OE and project primarily to a few glomeruli in the ventromedial region of the OB. The OE was lesioned by intranasal irrigation with Triton X-100, and the distribution of 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal)-stained cells was examined in the OE along with beta-galactosidase-immunoreactive (beta-gal-ir) axonal processes in the OB after short (1 week), intermediate (3 week), and long (6-7 weeks) recovery times. One week after the lesion, immunostaining for beta-gal and olfactory marker protein was virtually eliminated in the bulb. After 3 weeks of recovery, beta-gal-containing axons appeared to target many of the same locations innervated in bulbs of unlesioned mice. The region that received the highest density of axonal innervation in controls, however, contained only a few processes at that time. After 6-7 week recovery periods, the pattern of X-gal staining in the OE and beta-gal-ir axons in the OB closely resembled that of unlesioned mice. These results demonstrate that the topographic distribution of ORNs in the OE and the pattern of axon innervation in the OB can be reconstituted after chemical deafferentation.

Animals↗
PubMed2000

The role of segmentation in phonological processing: an fMRI investigation.

Phonological processes map sound information onto higher levels of language processing and provide the mechanisms by which verbal information can be temporarily stored in working memory. Despite a strong convergence of data suggesting both left lateralization and distributed encoding in the anterior and posterior perisylvian language areas, the nature and brain encoding of phonological subprocesses remain ambiguous. The present study used functional magnetic resonance imaging (fMRI) to investigate the conditions under which anterior (lateral frontal) areas are activated during speech-discrimination tasks that differ in segmental processing demands. In two experiments, subjects performed "same/ different" judgments on the first sound of pairs of words. In the first experiment, the speech stimuli did not require overt segmentation of the initial consonant from the rest of the word, since the "different" pairs only varied in the phonetic voicing of the initial consonant (e.g., dip-tip). In the second experiment, the speech stimuli required segmentation since "different" pairs both varied in initial consonant voicing and contained different vowels and final consonants (e.g., dip-ten). These speech conditions were compared to a tone-discrimination control condition. Behavioral data showed that subjects were highly accurate in both experiments, but revealed different patterns of reaction-time latencies between the two experiments. The imaging data indicated that whereas both speech conditions showed superior temporal activation when compared to tone discrimination, only the second experiment showed consistent evidence of frontal activity. Taken together, the results of Experiments 1 and 2 suggest that phonological processing per se does not necessarily recruit frontal areas. We postulate that frontal activation is a product of segmentation processes in speech perception, or alternatively, working memory demands required for such processing.

Adult↗
PubMed1998

Different neural circuits subserve reading before and after therapy for acquired dyslexia.

Rehabilitative measures for stroke are not generally based on basic neurobiological principles, despite evidence from animal models that certain anatomical and pharmacological changes correlate with recovery. In this report, we use functional magnetic resonance imaging (fMRI) to study in vivo human brain reorganization in a right handed patient with an acquired reading disorder from stroke. With phonological dyslexia, her whole-word (lexical) reading approach included inability to read nonwords and poor reading of function words. Following therapy, she was able to read nonwords and function words, and preferred a decompositional (sub-lexical) strategy in general. fMRI was performed during a reading task before and after treatment. Prior to therapy, her main focus of brain activation was in the left angular gyrus (area 39). After therapy, it was instead in the left lingual gyrus (area 18). This result suggests first that it is possible to alter brain physiology with therapy for acquired language disorders, and second, that two reading strategies commonly used in normal reading use distinct neural circuits, possibly reconciling several conflicting neuroimaging studies of reading.

Adult↗
PubMed1998

Suppression of vascular artifacts in functional magnetic resonance images using MR angiograms.

This paper describes a method for processing functional magnetic resonance images that suppresses signal changes originating from macroscopic veins visible in acquired magnetic resonance angiograms. Finger tapping experiments were performed on a 1.5-T scanner and the response was evaluated with voxel-by-voxel cross-correlation of the time course with a sinusoid at the paradigm frequency. After applying a vascular mask to suppress signal changes under macroscopic vessels, the vascular and nonvascular subpopulations of the data were compared. By visual inspection, the method was found to remove extracortical activation while preserving activation in the parenchyma. The observed higher signal amplitudes and temporal phase lags of the vascular population agree with theoretical models and previous studies. A significant portion of negatively correlated voxels occurs adjacent to through-plane vessels. Finally, comparing the centers of mass of the activated area before and after vascular suppression showed significant shifts in some subjects.

Artifacts↗
PubMed1997

A model of ocular dominance column development by competition for trophic factor.

Recent experimental evidence has shown that application of certain neurotrophic factors (NTs) to the developing primary visual cortex prevents the development of ocular dominance (OD) columns. One interpretation of this result is that afferents from the lateral geniculate nucleus compete for postsynaptic trophic factor in an activity-dependent manner. Application of excess trophic factor eliminates this competition, thereby preventing OD column formation. We present a model of OD column development, incorporating Hebbian synaptic modification and activity-driven competition for NT, which accounts for both normal OD column development as well as the prevention of that development when competition is removed. In the "control" situation, when available NT is below a critical amount, OD columns form normally. These columns form without weight normalization procedures and in the presence of positive inter-eye correlations. In the "experimental" case, OD column development is prevented in a local neighborhood in which excess NT has been added. Our model proposes a biologically plausible mechanism for competition between neural populations that is motivated by several pieces of experimental data, thereby accounting for both normal and experimentally perturbed conditions.

Animals↗
PubMed1997

Semantic category imprecision: a connectionist study of the boundaries of word meanings.

The view that word meanings have a discrete symbolic character has led to misleading impressions about their neurobiological basis. We hypothesize that this lexical semantic knowledge is imprecise, overlapping, and widely distributed throughout the human temporal lobes. The present study uses a computer modeling experiment to investigate this hypothesis. The objects in the study are "cups" and "bowls." Thirty connectionist networks were taught that wide containers without handles are "bowls" and that narrow containers with handles are "cups." The network was then asked to identify 14 different cylindrical containers of seven different widths, some with handles and others without. When compared to a study of human performance, the networks manifested the normal pattern of object naming and the normal pattern of individual variability.

Computers↗
PubMed1997

Subcortical aphasia and the problem of attributing functional responsibility to parts of distributed brain processes.

N&C's discussion is, in places, an exemplar of the sort of rigor and attention to detail that will bring us closer to an understanding of the functional organization of the brain. Indeed, it is this level of work that pushes us to reflect on the assumptions that undergird our research efforts. Our criticisms have developed four main points. First, the level of rigor applied to the consideration of basal ganglionic aphasia should extend to each application of the CPC method (thalamic aphasia included). Second, in our haste to identify specific brain systems with distinct cognitive functions we should not neglect the more basic question of the causal mechanisms by which the brain organizes behavior. Questions of "direct" versus "indirect" involvement of a particular organ in a cognitive function are only likely to distract our attention from this more basic and less inferentially perilous issue. Third, pure cases should no longer be considered touchstones against which all behavioral disturbances are measured. Reifying such ideals is more likely to shroud than reveal the brain's true complexity. Finally, the functions that we enshrine in particular brain regions should explain the particular character of the symptoms observed when they are damaged and should admit of independent verification.

Aphasia, Broca↗
PubMed1996

Localizing the lexicon for reading aloud:replication of a PET study using fMRI.

Functional magnetic resonance imaging (fMRI) was used to investigate the neural basis of written word recognition in two normal subjects. With a 1.5T scanner and temporal surface coil, T2 gradient echo images were obtained while subjects read words aloud. As a control condition, subjects visualized false font strings and said the word "range' each time such a string appeared. These two conditions were presented in an oscillatory pattern, alternating 30 s of each condition for a total of 4 min. Comparison of the two conditions using cross-correlation demonstrated strong activation in both subjects in the left posterior superior temporal gyrus, near the site predicted for the visual input lexicon by Déjerine and recently demonstrated by positron emission tomography.

Adult↗
PubMed1996

Immunosuppression-induced leukoencephalopathy from tacrolimus (FK506)

Tacrolimus (FK506) has recently been approved for immunosuppression in organ transplantation, although its use is accompanied by a wide spectrum of neurotoxic side effects. We describe the clinical, radiological, and pathological features of 3 cases of tacrolimus-related leukoencephalopathy. The syndrome of immunosuppression-related leukoencephalopathy is proposed as an uncommon neurological syndrome occurring in patients with organ transplants involving demyelination, in particular in the parieto-occipital region and centrum semiovale. Although the syndrome is not associated with a particular (absolute) serum level of tacrolimus, it resolves spontaneously upon decreasing the dose. The tacrolimus-related syndrome has a similar radiographic and pathologic appearance as the analogous syndrome that occurs in patients taking cyclosporine.

Adult↗
PubMed1996

Preoperative cortical localization with functional MRI for use in stereotactic radiosurgery.

Accurate localization of the lesion with respect to functionally significant brain is essential to safe stereotactic radiosurgical dose planning. We report the use of functional MR imaging in 3 patients to identify critical areas of surrounding brain and to provide assistance with dose planning, especially with regard to shaping the peripheral isodose around the lesion. We used a functional MRI system employing a conventional 1.5-tesla MRI unit that can detect decreases in deoxyhemoglobin concentration occurring with performance of specific tasks. Two of the patients had supratentorial arteriovenous malformations and 1 patient had a recurrent parasagittal meningioma. Functional MRI provided information on the location of speech, motor, and sensory cortex in these patients. Radiosurgical dose plans were constructed that kept these cortical areas outside of the 30% isodose curves. We believe that the safety of supratentorial parenchymal radiosurgery will be enhanced by the localization of critical brain regions around the target.

Adult↗