PubMed query for “Parkinson disease” yields more than 2,000 articles per year for each of the last 5 years. That is a daunting pile of bedside reading for even the most diligent neurologist. This review highlights 5 emerging topics that are changing our current understanding and management of Parkinson disease (PD). When using the term PD, we mean Lewy body parkinsonism as defined by the clinical criteria of the United Kingdom Parkinson's Disease Society Brain Bank. Other parkinsonian syndromes, such as progressive supranuclear palsy and multiple system atrophy, are beyond the scope of this review (Full text).
Approach to acute or subacute myelopathy
Improved understanding of the differential diagnosis and improved investigative techniques, particularly neuroimaging and serologic testing, have facilitated the diagnosis of patients with acute and subacute myelopathy and reduced the proportion of patients who are labeled as having “idiopathic transverse myelitis.” Additionally, these advances have identified subgroups of patients in whom progression of deficit or future relapses are anticipated, allowing intervention and prophylaxis as appropriate. However, early management remains empiric and consists of high-dose corticosteroids for most patients. In the event of an inadequate response to corticosteroids or a subsequent atypical course, further investigations to detect diagnoses other than “transverse myelitis” should be considered and additional treatments, such as plasmapheresis, may be appropriate. Individualized diagnosis and treatment is more feasible now than in the past (Full text).
Neurology November 1, 2010 vol. 75 no. 18 Supplement 1 S2-S8
Insular cortex
The insular taste cortex contributes to odor qualiting coding
Despite distinct peripheral and central pathways, stimulation of both the olfactory and the gustatory systems may give rise to the sensation of sweetness. Whether there is a common central mechanism producing sweet quality sensations or two discrete mechanisms associated independently with gustatory and olfactory stimuli is currently unknown. Here authors used fMRI to determine whether odor sweetness is represented in the piriform olfactory cortex, which is thought to code odor quality, or in the insular taste cortex, which is thought to code taste quality. Fifteen participants sampled two concentrations of a pure sweet taste (sucrose), two sweet food odors (chocolate and strawberry), and two sweet floral odors (lilac and rose). Replicating prior work we found that olfactory stimulation activated the piriform, orbitofrontal and insular cortices. Of these regions, only the insula also responded to sweet taste. More importantly, the magnitude of the response to the food odors, but not to the non-food odors, in this region of insula was positively correlated with odor sweetness rating. These findings demonstrate that insular taste cortex contributes to odor quality coding by representing the taste-like aspects of food odors. Since the effect was specific to the food odors, and only food odors are experienced with taste, authors suggest this common central mechanism develops as a function of experiencing flavors.
(A) Coronal and sagittal sections of the area of insula where neural response to the food odors shows a positive correlation with the sweetness ratings of those odors. The main images display the unmasked regression maps while the insets labeled 1 depict the masked regressions (i.e., using the “sweet odors and sweet taste overlap” inclusive mask). The insets labeled 2 depict the analysis with the pleasantness and familiarity ratings as covariates. (B) Shows neural response (in parameter estimate) in the insula (at the maximally responding voxel at −45 −3 9), plotted against sweetness ratings for the food (red squares) and floral odors (yellow diamonds). (C) Illustrates the magnitude of the correlation (averaged across all voxels ± standard deviation) in the insula for food odors (in red squares) and non-food odor (yellow diamonds) in comparison to the responses in other areas for food and non-food odors vs. odorless. Note that although there appears to be a significant difference between food and floral odors in the left OFC, this effect this effect does not survive authors' criterion for significance in SPM and is therefore not discussed.
Reference: Veldhuizen MG, Nachtigal D, Teulings L, Gitelman DR and Small DM (2010) The insular taste cortex contributes to odor quality coding. Front. Hum. Neurosci. 4:58. doi: 10.3389/fnhum.2010.00058
Occipital cortex
Investigating representations of facial identity in human ventral visual cortex with transcranial magnetic stimulation
The occipital face area (OFA) is face-selective. This enhanced activation to faces could reflect either generic face and shape-related processing or high-level conceptual processing of identity. Here authors examined these two possibilities using a state-dependent transcranial magnetic stimulation (TMS) paradigm. The lateral occipital (LO) cortex which is activated non-selectively by various types of objects served as a control site. They localized OFA and LO on a per-participant basis using functional MRI. They then examined whether TMS applied to either of these regions affected the ability of participants to decide whether two successively presented and physically different face images were of the same famous person or different famous people. TMS was applied during the delay between first and second face presentations to investigate whether neuronal populations in these regions played a causal role in mediating the behavioral effects of identity repetition. Behaviorally they found a robust identity repetition effect, with shorter reaction times (RTs) when identity was repeated, regardless of the fact that the pictures were physically different. Surprisingly, TMS applied over LO (but not OFA) modulated overall RTs, compared to the No-TMS condition. But critically, authors found no effects of TMS to either area that were modulated by identity repetition. Thus, they found no evidence to suggest that OFA or LO contain neuronal representations selective for the identity of famous faces which play a causal role in identity processing. Instead, these brain regions may be involved in the processing of more generic features of their preferred stimulus categories.
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Stimuli examples and pixel-wise differences. (A) Examples of repeated identity trials stimuli (blue frame) and different identity trials stimuli (red frame). The first presented face image appears on the left, the second on the right. Repeated identity trials depicting Michelle Obama (top) and Tom Hanks (bottom). Different identity trials depicting Al Pacino, Dustin Hoffman, Britney Spears, and Scarlett Johansson are shown. See the list of individuals in Table 1; please note that these are examples for illustrative purposes and the exact images used in the experiment are available on request from the authors. (B) Pixel-wise differences for repeated identity trials and different identity trials (see further details in Materials and Methods). No significant difference in low-level image differences was found between the trial types. (C) Examples from the post hoc stimuli analysis: all stimuli were cropped to restrict the picture to the face only and normalized to a common size (see further details in Materials and Methods). (D) Pixel-wise differences as in (B) for the normalized images (described in C). |
Reference: Gilaie-Dotan S, Silvanto J, Schwarzkopf DS and Rees G (2010) Investigating representations of facial identity in human ventral visual cortex with transcranial magnetic stimulation. Front. Hum. Neurosci.4:50. doi: 10.3389/fnhum.2010.00050
Mapping psychiatric disorders
Mapping synaptic pathology within cerebral cortical circuits in subjects with schizophrenia
Converging lines of evidence indicate that schizophrenia is characterized by impairments of synaptic machinery within cerebral cortical circuits. Efforts to localize these alterations in brain tissue from subjects with schizophrenia have frequently been limited to the quantification of structures that are non-selectively identified (e.g., dendritic spines labeled in Golgi preparations, axon boutons labeled with synaptophysin), or to quantification of proteins using methods unable to resolve relevant cellular compartments. Multiple label fluorescence confocal microscopy represents a means to circumvent many of these limitations, by concurrently extracting information regarding the number, morphology, and relative protein content of synaptic structures. An important adaptation required for studies of human disease is coupling this approach to stereologic methods for systematic random sampling of relevant brain regions. In this review article authors consider the application of multiple label fluorescence confocal microscopy to the mapping of synaptic alterations in subjects with schizophrenia and describe the application of a novel, readily automated, iterative intensity/morphological segmentation algorithm for the extraction of information regarding synaptic structure number, size, and relative protein level from tissue sections obtained using unbiased stereological principles of sampling. In this context, authors provide examples of the examination of pre- and post-synaptic structures within excitatory and inhibitory circuits of the cerebral cortex.
Converging lines of evidence indicate that schizophrenia is characterized by impairments of synaptic machinery within cerebral cortical circuits. Efforts to localize these alterations in brain tissue from subjects with schizophrenia have frequently been limited to the quantification of structures that are non-selectively identified (e.g., dendritic spines labeled in Golgi preparations, axon boutons labeled with synaptophysin), or to quantification of proteins using methods unable to resolve relevant cellular compartments. Multiple label fluorescence confocal microscopy represents a means to circumvent many of these limitations, by concurrently extracting information regarding the number, morphology, and relative protein content of synaptic structures. An important adaptation required for studies of human disease is coupling this approach to stereologic methods for systematic random sampling of relevant brain regions. In this review article authors consider the application of multiple label fluorescence confocal microscopy to the mapping of synaptic alterations in subjects with schizophrenia and describe the application of a novel, readily automated, iterative intensity/morphological segmentation algorithm for the extraction of information regarding synaptic structure number, size, and relative protein level from tissue sections obtained using unbiased stereological principles of sampling. In this context, authors provide examples of the examination of pre- and post-synaptic structures within excitatory and inhibitory circuits of the cerebral cortex.
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| (A). A schematic of a human brain, showing the superior temporal gyrus (STG) which can be sampled systematic uniformly random, shown here as a series of numbered blocks from which every other block (yellow) is selected for further processing. (B) Each of the selected blocks is further subsampled into a systematic random series of sections for microscopy [shown here for one of the blocks, with every other section in this example selected for further processing (yellow)]. (C) Within each sampled section the region of interest is identified (e.g., shown here as the yellow outline of deep layer 3 within the larger cytoarchitectonically defined Primary Auditory Cortex area of interest shown in dark gray). (D) An enlarged view of a portion of the region of interest showing a systematic random sampling grid which has been placed over each sampled section. Sites for microscopic sampling are identified by each grid intersection with the region of interest. (E) An enlarged view of a single sampling site, showing the optical disector located within the z-axis of the tissue section. The gray outlines represent the projections of the disector unto the superficial and deep surfaces of the tissue section. (F) A series of 2D confocal images at a fixed distance apart in the z-axis (see Other Technical Issues for a discussion of appropriate z-axis sampling distances) are collected at each sampling site. Immunoreactive synaptic structures are shown as red puncta. (G) The series of images are combined to form a 3D data set from each site, resulting in a sampled cube with x and y dimensions represented here in pixels and the z dimension as plane number. Within this data set, the disector can be conceived of as defined by a set of values in 3D. (H) Using the masking approach described above, a center of volume, that is a single point defined by x, y, z coordinates, can be assigned for each immunoreactive puncta. Puncta with centers of volume falling within the boundaries of the optical disector are sampled for quantification (shown here in green), while those puncta with centers of volume falling outside the disector, or touching one of the exclusion lines (red) are not selected for quantification. SF, Sylvian fissure; STS, superior temporal sulcus. |
Speech
Hierarchical models of processing intelligible speech
There is now consensus that hierarchical processing is a key organizational aspect of the human cortical auditory system. Challenges for future studies include placing hierarchical organization in the temporal lobe within the broader context of larger networks for auditory and language processing, and clarifying the functional contribution of different parallel auditory processing pathways to comprehension of spoken language under varying degrees of effort.
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| (A) Hierarchical processing in the temporal lobe, showing a posterior-anterior gradient in acoustic insensitivity moving away from primary auditory cortex. Posterior and anterior regions of STS discussed by Okada et al. (2010) are outlined in white. (B) An expanded model of hierarchical processing for speech that includes prefrontal, premotor/motor, and posterior inferotemporal regions. |
Reference: Peelle JE, Johnsrude IS and Davis MH (2010) Hierarchical processing for speech in human auditory cortex and beyond. Front. Hum. Neurosci. 4:51. doi: 10.3389/fnhum.2010.00051
Cognitive rehabilitation
Cognitive rehabilitation of episodic memory disorders: from theory to practice
Memory disorders are among the most frequent and most debilitating cognitive impairments following acquired brain damage. Cognitive remediation strategies attempt to restore lost memory capacity, provide compensatory techniques or teach the use of external memory aids. Memory rehabilitation has strongly been influenced by memory theory, and the interaction between both has stimulated the development of techniques such as spaced retrieval, vanishing cues or errorless learning. These techniques partly rely on implicit memory and therefore enable even patients with dense amnesia to acquire new information. However, knowledge acquired in this way is often strongly domain-specific and inflexible. In addition, individual patients with amnesia respond differently to distinct interventions. The factors underlying these differences have not yet been identified. Behavioral management of memory failures therefore often relies on a careful description of environmental factors and measurement of associated behavioral disorders such as unawareness of memory failures. The current evidence suggests that patients with less severe disorders benefit from self-management techniques and mnemonics whereas rehabilitation of severely amnesic patients should focus on behavior management, the transmission of domain-specific knowledge through implicit memory processes and the compensation for memory deficits with memory aids.
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| Learning capacity, spatio-temporal orientation, awareness of the deficit, and independence in activities of daily living (ADL) as a function of the degree of memory impairment (click on the table to enlarge). |
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