Verbal semantics and the left dorsolateral anterior temporal lobe: a longitudinal case of bilateral temporal degeneration

ABSTRACT

Background

Semantic variant primary progressive aphasia (svPPA), a clinical syndrome characterized by loss of semantic knowledge, is associated with neurodegeneration that starts in the anterior temporal lobe (ATL) and gradually spreads towards posterior temporal and medial frontal areas. At the earliest stages, atrophy may be predominantly lateralized to either the left or right ATL, leading to different clinical profiles with the greatest impairment of word comprehension or visual/social semantics, respectively.

Methods & Procedures

We report the in-depth longitudinal investigation of cognitive and neuroanatomical features of JB, an unusual case of ATL neurodegeneration with relative sparing of left lateral ATL regions.

Outcomes & Results

Over the course of 9 years, neurodegeneration progressed to involve bilateral temporo-lateral and frontal regions, resulting in a relatively symmetric and diffuse frontotemporal atrophy pattern. In parallel, JB developed greater behavioral, cognitive, and language impairments, as well as signs of motor neuron disease at her last evaluation. Episodic memory and socio-emotional processing deficits arose, likely secondary to semantic verbal deficits, while visuospatial processing, executive function, and non-semantic language abilities remained largely unaffected throughout the course of the disease.

Conclusions

The details of this rare case of early medial more than lateral ATL degeneration are consistent with a bilateral organization of the semantic system and, crucially, with a functional dissociation between medial paralimbic and lateral neocortical temporal regions. Cases of frontotemporal dementia (FTD) such as JB, who initially do not meet current clinical criteria for svPPA and instead present with some features of behavioral variant FTD, highlight the need for specific criteria for the right temporal variant of FTD that we propose could be called semantic variant FTD.

KEYWORDS:

• Primary progressive aphasia
• semantic dementia
• right temporal variant
• frontotemporal dementia
• motor neuron disease

Acknowledgments

This work was funded by the National Institutes of Health (M.GT., NINDS R01 NS050915), (M.GT., NIDCD K24 DC015544), (B.M., NIA P50 AG023501), and by Alzheimer Nederland (J.V.). We thank JB and her family for their time and effort dedicated to our research. We kindly thank Grace Rice and Matthew Lambon Ralph for providing control data of the Over-regular Object Test.

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed here.

Notes

1. These analyses were performed using the in-house Brainsight system, developed at UCSF by Katherine P. Rankin, Cosmo Mielke, and Paul Sukhanov, and powered by the VLSM script written by Stephen M. Wilson, with funding from the Rainwater Charitable Foundation and the UCSF Chancellor’s Fund for Precision Medicine.

Additional information

Funding

This work was supported by the National Institute of Neurological Disorders and Stroke [R01 NS050915]; National Institute on Aging [P50 AG023501]; National Institute on Deafness and Other Communication Disorders [K24 DC015544]; Alzheimer Nederland.