Domenico Montanaro

Ultra-High-Field MR Imaging in Polymicrogyria and Epilepsy

BACKGROUND AND PURPOSE: Polymicrogyria is a malformation of cortical development that is often identified in children with epilepsy or delayed development. We investigated in vivo the potential of 7T imaging in characterizing polymicrogyria to determine whether additional features could be identified. MATERIALS AND METHODS: Ten adult patients with polymicrogyria previously diagnosed by using 3T MR imaging underwent additional imaging at 7T. We assessed polymicrogyria according to topographic pattern, extent, symmetry, and morphology. Additional imaging sequences at 7T included 3D T2* susceptibility-weighted angiography and 2D tissue border enhancement FSE inversion recovery. Minimum intensity projections were used to assess the potential of the susceptibility-weighted angiography sequence for depiction of cerebral veins. RESULTS: At 7T, we observed perisylvian polymicrogyria that was bilateral in 6 patients, unilateral in 3, and diffuse in 1. Four of the 6 bilateral abnormalities had been considered unilateral at 3T. While 3T imaging revealed 2 morphologic categories (coarse, delicate), 7T susceptibility-weighted angiography images disclosed a uniform ribbonlike pattern. Susceptibility-weighted angiography revealed numerous dilated superficial veins in all polymicrogyric areas. Tissue border enhancement imaging depicted a hypointense line corresponding to the gray-white interface, providing a high definition of the borders and, thereby, improving detection of the polymicrogyric cortex. CONCLUSIONS: 7T imaging reveals more anatomic details of polymicrogyria compared with 3T conventional sequences, with potential implications for diagnosis, genetic studies, and surgical treatment of associated epilepsy. Abnormalities of cortical veins may suggest a role for vascular dysgenesis in pathogenesis.

A case of amnesia at an early age

A dissociation between short- and long-term memory (LTM) and between the episodic and the semantic component of LTM is reported in a young girl who became amnesic at the age of 6 after an episode of acute encephalopathy resulting in bilateral frontal, insular, thalamic, ponto-mesencephalic, hippocampal and temporal lesions, as documented by MRI. The girl became amnesic a few months after starting school. A follow-up investigation showed that she was able to learn to read, write and acquire number facts and procedures and to improve her semantic knowledge. Our results show that the features of adult amnesia can also be found in children and that new semantic knowledge can be acquired in spite of an anterograde memory deficit. This dissociation does not agree with theories viewing long-term declarative memory as a unitary process mediated by the hippocampal system, but supports recent hypotheses that the acquisition of semantic knowledge is independent from episodic memory processes, and takes place through spared cortical regions subjacent to the hippocampi (Vargha-Khadem et al., 1997).

Reorganisation of the sensorimotor cortex after early focal brain lesion: a functional MRI study in monozygotic twins

Sensorimotor cortical reorganization after early brain lesions was studied by means of fMRI in two pairs of monozygotic twins, in each of which one member had a focal brain injury. This offered a unique opportunity to reduce the wide intersubject variability of the controls often found in similar studies. Activation images were acquired during a motor task (sequential opposition finger movements) and a sensory task (passive brushing of palm and fingers). During the tasks with the recovered hand, constant findings in the lesioned subjects were the activation of the undamaged areas adjacent to lesion site and the activation of the ipsilateral sensorimotor cortex. Bilateral activation of the primary sensorimotor cortex was never observed in the healthy co-twin controls.

BOLD response to spatial phase congruency in human brain

Human psychophysical observations, computational models, and the selectivity of neurons in primary visual cortex all suggest that an early step in visual processing is the detection of features such as lines and edges. However, previous fMRI experiments investigating the responses of early visual areas to phase coherence have led to apparently discordant results. We studied the human brain BOLD responses to structured periodic band-pass images of matched amplitude spectrum but of different phase spectra, arranged to create three distinct types of stimuli: pure edges; pure lines (matched global and local energy to the edges, but different phase); and random noise (random phase spectrum, hence no salient features, and a different spatial distribution of local energy from the lines and edges stimuli). Alternation of lines against edges did not activate primary visual cortex, but did activate two higher order visual areas. Alternation of these lines or edges against the random stimulus produced a strong activity in many visual areas, including primary visual cortex. Interestingly, the BOLD activity was higher for the edges and lines than for the random stimuli for a wide range of stimulus contrasts, indicating the presence of non-linear gain modulation in the cell response. These results show that phase congruency is coded at the level of primary visual cortex. We show that a stage of response gain modulation can explain our present and previous fMRI discordant results.

Focal cortical dysplasia type IIb in the rolandic cortex: Functional reorganization after early surgery documented by passive task functional MRI

Surgery for seizures arising from the rolandic area can be performed effectively, and accurate mapping of eloquent regions may improve seizure and functional outcome. Noninvasive cortical mapping is, however, hardly feasible in young children. We studied two children with epileptogenic focal cortical dysplasia (FCD) type IIb in the rolandic area, in whom preoperative passive task functional MRI (fMRI) during sedation helped planning a tailored surgical approach. In one patient the dysplastic cortex was functionally activated. After complete lesionectomy both children exhibited motor impairment that readily improved. Repeat fMRI, performed after complete (Patient 1) or partial (Patient 2) recovery, demonstrated relocation of motor‐related activations posterior to the area of resection. fMRI during sedation can be used to demonstrate postsurgical functional reorganization of the motor cortex in young children. There is interindividual variability in functional activation of FCD type IIb.

Laser nephelometric evaluation of albumin, IgG and α2-macroglobulin: applications to the study of alterations of the blood-brain barrier

Cerebrospinal fluid and serum levels of albumin, immunoglobulin G and alpha 2-macroglobulin were determined by laser nephelometer in various pathological conditions: Guillain-Barré syndrome amyotrophic lateral sclerosis, lumbar disc herniation. These proteins are different due to their molecular weight, spacial conformation, CSF and serum concentrations and their CSF/serum quotient reflects the status of the blood-brain barrier. In the subjects group comparisons, albumin quotient and IgG quotient show a significant differentiations. The linear regression of albumin quotient compared to alpha 2-macroglobulin quotient behaves differently in the individual groups. The protein CSF/serum quotients are helpful in distinguishing the causes of alterations in the blood-brain barrier.

BOLD human responses to chromatic spatial features

Animal physiological and human psychophysical studies suggest that an early step in visual processing involves the detection and identification of features such as lines and edges, by neural mechanisms with even‐ and odd‐symmetric receptive fields. Functional imaging studies also demonstrate mechanisms with even‐ and odd‐receptive fields in early visual areas, in response to luminance‐modulated stimuli. In this study we measured fMRI BOLD responses to 2‐D stimuli composed of only even or only odd symmetric features, and to an amplitude‐matched random noise control, modulated in red–green equiluminant colour contrast. All these stimuli had identical power but different phase spectra, either highly congruent (even or odd symmetry stimuli) or random (noise). At equiluminance, V1 BOLD activity showed no preference between congruent‐ and random‐phase stimuli, as well as no preference between even and odd symmetric stimuli. Areas higher in the visual hierarchy, both along the dorsal pathway (caudal part of the intraparietal sulcus, dorsal LO and V3A) and the ventral pathway (V4), responded preferentially to odd symmetry over even symmetry stimuli, and to congruent over random phase stimuli. Interestingly, V1 showed an equal increase in BOLD activity at each alternation between stimuli of different symmetry, suggesting the existence of specialised mechanisms for the detection of edges and lines such as even‐ and odd‐chromatic receptive fields. Overall the results indicate a high selectivity of colour‐selective neurons to spatial phase along both the dorsal and the ventral pathways in humans.

Inversion of perceived direction of motion caused by spatial undersampling in two children with periventricular leukomalacia

We report here two cases of two young diplegic patients with cystic periventricular leukomalacia who systematically, and with high sensitivity, perceive translational motion of a random-dot display in the opposite direction. The apparent inversion was specific for translation motion: Rotation and expansion motion were perceived correctly, with normal sensitivity. It was also specific for random-dot patterns, not occurring with gratings. For the one patient that we were able to test extensively, contrast sensitivity for static stimuli was normal, but was very low for direction discrimination at high spatial frequencies and all temporal frequencies. His optokinetic nystagmus movements were normal but he was unable to track a single translating target, indicating a perceptual origin of the tracking deficit. The severe deficit for motion perception was also evident in the seminatural situation of a driving simulation video game. The perceptual deficit for translational motion was reinforced by functional magnetic resonance imaging studies. Translational motion elicited no response in the MT complex, although it did produce a strong response in many visual areas when contrasted with blank stimuli. However, radial and rotational motion produced a normal pattern of activation in a subregion of the MT complex. These data reinforce the existent evidence for independent cortical processing for translational, and circular or radial flow motion, and further suggest that the two systems have different vulnerability and plasticity to prenatal damage. They also highlight the complexity of visual motion perception, and how the delicate balance of neural activity can lead to paradoxical effects such as consistent misperception of the direction of motion. We advance a possible explanation of a reduced spatial sampling of the motion stimuli and report a simple model that simulates well the experimental results.

Plasticity of the human visual brain after an early cortical lesion

In adults, partial damage to V1 or optic radiations abolishes perception in the corresponding part of the visual field, causing a scotoma. However, it is widely accepted that the developing cortex has superior capacities to reorganize following an early lesion to endorse adaptive plasticity. Here we report a single patient case (G.S.) with near normal central field vision despite a massive unilateral lesion to the optic radiations acquired early in life. The patient underwent surgical removal of a right hemisphere parieto-temporal-occipital atypical choroid plexus papilloma of the right lateral ventricle at four months of age, which presumably altered the visual pathways during in utero development. Both the tumor and surgery severely compromised the optic radiations. Residual vision of G.S. was tested psychophysically when the patient was 7 years old. We found a close-to-normal visual acuity and contrast sensitivity within the central 25° and a great impairment in form and contrast vision in the far periphery (40-50°) of the left visual hemifield. BOLD response to full field luminance flicker was recorded from the primary visual cortex (V1) and in a region in the residual temporal-occipital region, presumably corresponding to the middle temporal complex (MT+), of the lesioned (right) hemisphere. A population receptive field analysis of the BOLD responses to contrast modulated stimuli revealed a retinotopic organization just for the MT+ region but not for the calcarine regions. Interestingly, consistent islands of ipsilateral activity were found in MT+ and in the parieto-occipital sulcus (POS) of the intact hemisphere. Probabilistic tractography revealed that optic radiations between LGN and V1 were very sparse in the lesioned hemisphere consistently with the post-surgery cerebral resection, while normal in the intact hemisphere. On the other hand, strong structural connections between MT+ and LGN were found in the lesioned hemisphere, while the equivalent tract in the spared hemisphere showed minimal structural connectivity. These results suggest that during development of the pathological brain, abnormal thalamic projections can lead to functional cortical changes, which may mediate functional recovery of vision.

Clinical and paraclinical indicators of motor system impairment in hereditary spastic paraplegia: A pilot study

Background Hereditary spastic paraplegias (HSP) are a composite and genetically heterogeneous group of conditions mainly expressed by the impairment of the central motor system (“pure” forms). The involvement of other components of the central nervous system or of other systems is described in the “complicate” forms. The definition of an investigation protocol capable, by assembling clinical and paraclinical indicators to fully represent the extent of the motor system impairment, would help both the clinical handling of these conditions and contribute to our understanding of their pathogenesis. Methods We applied a clinical and paraclinical protocol which included tools exploring motor and non motor functioning, neurophysiology and MRI to a composite cohort of 70 molecularly defined HSP patients aged 3 to 65, to define for each indicator its significance in detailing the presence and the severity of the pathology. Results Clinically increased deep tendon reflexes and lower limb (LL) weakness are constant findings in all patients. The “complicated” forms are characterized by peripheral motor impairment, cognitive and cerebellar involvement. The Spastic Paraplegia Rating Scale efficiently reflects the severity of functional problems and correlates with disease duration. Neurophysiology consistently documents the impairment of the central motor pathway to the LLs. Nevertheless, the upper extremities and sensory system involvement is a frequent finding. MRI diffusion tensor imaging (DTI) highlighted a significant alteration of FA and MD. Combining the sampling of the various portion of the cortico-spinal tract (CST) DTI consistently discriminated patients from controls. Conclusion We propose a graded clinical and paraclinical protocol for HSP phenotype definition, indicating for each tool the discriminative and descriptive capacity. Our protocol applied to 9 different forms of HSP showed that the functional impairment often extends beyond the CST. The novel DTI approach may add significant elements in disease recognition, staging and mapping.