For Clinicians and Scientists

A significant discrepancy between verbal comprehension and perceptual reasoning abilities, in which verbal skills are greater than perceptual skills, is a necessary feature to make the NVLD diagnosis, but it is not sufficient in the absence of sustained academic, professional, social, and emotional difficulties.

Children with NVLD have strengths in verbal reasoning, such as a well-developed vocabulary, rote learning skills, strong factual recall when information is presented without context, and remembering concrete details from a story. In contrast, they have trouble understanding the “big picture” and identifying the main idea in a narrative. Children with NVLD also struggle with life skills that require an understanding of spatial relationships, such as recognizing how parts fit together into a whole, completing jigsaw puzzles and building with blocks, learning routes for travel, and manipulating objects in space.

Children with NVLD have trouble developing fine-motor skills and may have poor handwriting, difficulty learning to tie their shoelaces, and problems using small tools and utensils.

Children with NVLD may have weak executive functions or difficulty sustaining their attention. However, whether these problems are essential attributes of NVLD, or are simply common co-occurring issues in children who come to clinical attention, is unknown. These children may have trouble handling new tasks, solving problems and remaining flexible in their thinking. They may also have difficulty staying focused, completing multi-step instructions, organizing tasks and materials, controlling their impulses, and they may have other symptoms associated with Attention-Deficit/Hyperactivity Disorder (ADHD).

Children with NVLD are usually interested in social relationships and have the capacity for empathy, but may report feeling isolated and complain that they do not have satisfying relationships with their peers. Children with NVLD can have trouble understanding humor, which may contribute to their social problems. Clinicians believe that children with NVLD may suffer from depression and anxiety disorders more than children without NVLD, although this clinical impression currently lacks strong empirical support. A significant discrepancy between verbal comprehension and perceptual reasoning abilities, in which verbal skills are greater than perceptual skills, is a necessary feature to make the NVLD diagnosis.

Children with NVLD may have difficulty learning math concepts and procedures. In early years of school they may have trouble with numerocity, telling time, the value of coins, and greater-than and less-than relationships. In later years they may have problems translating fractions to decimals and associated procedures. Identifying and describing geometric shapes and reading graphs and charts may be difficult for children with NVLD. Children with NVLD may have trouble with certain language-based tasks in school that require understanding the big picture or solving new problems. For example, beginning in 3rd or 4th grade, they may have trouble with reading comprehension, as opposed to in earlier years when the focus was on sounding out words and the structure of stories. Children with NVLD may have a hard time answering inferential questions about literature. They also may have problems interpreting metaphors and understanding multiple meanings of words in a text. For similar reasons, they may have difficulty writing essays and trouble identifying information and evidence that support their point of view or thesis.

Our goal to demonstrate that NVLD is a valid diagnostic construct has motivated two complementary lines of study in our research program: (1) assessing NVLD symptoms in representative, community samples of children to identify the true clinical and behavioral presentations of NVLD and to determine whether these distinguish NVLD from other disorders; and (2) neuroimaging studies to identify the neurobiological underpinnings of NVLD and to distinguish them from those of other disorders.

Prior research on the clinical, cognitive, and behavioral features of NVLD has nearly always identified children from clinical samples who have a constellation of symptoms that have been regarded, from prior clinical impressions, to distinguish them from other children. Most studies then correlate diagnosis (either NVLD or a control group) with clinical variables. To summarize these studies somewhat crudely, those correlations show that the NVLD group has more symptoms of NVLD and other problems. It is not surprising that they have more NVLD symptoms than a control group since the NVLD group was selected on the basis of having those symptoms. That the NVLD group has additional problems at higher rates than in the control group is also not surprising. Berkson* showed long ago that any clinically identified population will have more problems than a non-clinical control population. Much of the prior work that has attempted to define the core clinical features of NVLD has therefore been largely tautological. In order to move away from this problematic tautology for defining and validating the core clinical features of NVLD, we need to assess whether the symptoms long thought to clinically define NVLD occur together more than by chance in samples of children who are not preselected to have those symptoms. The NVLD Project’s research program is therefore asking this question in large samples of representative children from community samples of participants who have undergone detailed cognitive and neuropsychiatric assessments. Based on a review of prior literature and on the basic conceptualization of NVLD as a condition in which spatial cognition is poor in relation to verbal abilities, we postulate that one defining criterion for the condition is the presence of a discrepancy between perceptual reasoning (formerly Performance IQ) and verbal comprehension (formerly Verbal IQ), as measured by intelligence tests. Therefore, in our community samples we are assessing whether the difference between these measures (the VIQ-PIQ discrepancy) correlates significantly with the presence of other cognitive, behavioral, and clinical problems. If NVLD is a valid classifiable construct, then the VIQ-PIQ difference should be accompanied by other problems. Our studies will test that hypothesis and determine whether the clinical features identified anecdotally in prior literature truly are co-occurring problems in children with NVLD. Moreover, conducting our studies in representative community samples will allow us to estimate the prevalence of NVLD in the general population. *J BERKSON. LIMITATION OF THE APPLICATION OF FOURFOLD TABLE ANALYSIS TO HOSPITAL DATA. BIOMEDICAL BULLETIN. 2: 47-53, 1946 Much of the prior work that has attempted to define the core clinical features of NVLD has been largely tautological.

Neuroimaging research provides information about the structure, function, and connectivity of neural structures and circuits. These structures and circuits support cognition. Disruption of these structures and circuits can lead to psychiatric illness. Our neuroimaging research program aims to understand the neurobiological underpinnings of NVLD. The VIQ-PIQ discrepancy is the single agreed upon feature that is necessary for a diagnosis of NVLD. Just as assessing the behavioral and clinical correlations of the VIQ-PIQ difference is most informative and valid in community samples (as discussed above), assessing the neurobiological correlates of the VIQ-PIQ difference is likewise most informative and valid in community samples of non-clinically identified individuals. In our recent paper we assessed the correlation of cortical thickness with the magnitude of the VIQ-PIQ difference in two independent samples of healthy human participants (N=83 and N=58, ages 5-57 years). We demonstrated that structural features of the brain that are associated with the VIQ-PIQ discrepancy in healthy individuals are not isolated in the brain’s right hemisphere, but are represented in both hemispheres. A progressively thinner cortical mantle in anterior and posterior regions bilaterally was associated with progressively greater (more positive) VIQ-PIQ difference scores. A progressively thicker cortical mantle in anterior and posterior regions bilaterally was associated with progressively greater (more positive) VIQ-PIQ difference scores. Variation in cortical thickness in these regions accounted for a large portion of the overall variance in magnitude of the VIQ-PIQ discrepancy. Thus, in healthy individuals the VIQ-PIQ discrepancy derives from bilateral sources in the brain. Although some researchers theorize that NVLD arises from right hemisphere dysfunction and reduced volumes of right hemisphere white matter, no empirical evidence substantiates that claim. Significance maps showing correlations of Cortical Thickness (CT) with VIQ-regressed-on-PIQ (left panel) and with PIQ-regressed-on-VIQ (right panel), corrected for multiple comparisons. At each point on the cerebral surface, the statistical significance (probability values) of the correlation of the VIQ-regressed-on-PIQ, and PIQ-regressed-on-VIQ score with CT is color-coded. Warm colors (yellow, orange, red) represent a positive correlation (thicker cortex as the residual score increases) and cooler colors (blue and purple) represent a negative correlation (thinner cortex as the residual score increases). (Upper) Maps of sample 1, N=83. (Lower) Maps of sample 2, N=58. In addition to evaluating structural correlates of the VIQ-PIQ difference, we are also assessing the functional and neurochemical correlates of the VIQ-PIQ difference in the brains of healthy, non-clinically identified individuals. These measures are acquired using the MRI modalities of functional MRI, Diffusion Tensor Imaging, Perfusion Imaging, and Magnetic Resonance Spectroscopy. Finally, we are beginning MRI studies of children who have been diagnosed clinically with NVLD to determine whether their brains have the same features, relative to healthy children, as we are identifying in our community-based samples. Identifying similar features in their brains would help validate NVLD as a distinct construct, suggesting that it is neurobiologically at one extreme of a continuum of VIQ-PIQ differences found in the general population.

Beatrice Beebe, Ph.D., a researcher for The NVLD Project, directs a basic research lab studying 4- and 12-month mother-infant communication, prior to the infant’s development of language. Infants’ pre-verbal learning of communication patterns lay the foundation for emotional and cognitive development for the rest of their lives. The lab specializes in the microanalysis of face-to-face non-verbal communication. Resources at the lab include a split-screen video-recording and audio-recording studio and an open play space for observing infants and children with their parents. Our research program investigates the dyadic non-verbal mechanisms that organize mother-infant social communication, the role that infant and maternal distress play in this communication, the effects of early mother-infant communication patterns on emerging infant and childhood attachment styles, and the long-term continuity of non-verbal communication and attachment styles from infancy to young adulthood. Our research for The NVLD Project concerns microanalysis of non-verbal communication in 4-month mother-infant interactions to understand the precursors of NVLD. Infants’ pre-verbal learning of communication patterns lay the foundation for emotional and cognitive development for the rest of their lives.