This report demonstrates the potential utility of the FMAER for study of children with language disorders. Six advances result from the investigation:
First, the findings constitute the first demonstration by use of discrete source analysis that the FMAER arises symmetrically from the bilateral posterior superior temporal lobes for neurotypical controls and patients with normal language function. Involved areas include primarily the planum temporale, posterior superior temporal gyrus, and to a more variable extent the middle temporal gyrus. These locations were consistently identified across all ten neurotypical subjects evaluated as well as the five clinical subjects with normal language function (Figure
6). Moreover, when FMAER data were obtained directly from the cortex of patients undergoing Phase 2 pre-surgical epilepsy evaluations, the same general cortical regions appeared active (Figures
Second, for epilepsy surgical cases the cortically recorded FMAER delineates putative language eloquent cortex should such delineation prove difficult with traditional techniques of cortical stimulation for various reasons as discussed above (see Figures
8). Cortical FMAER localization is generally consistent with the regions predicted by FMAER source analysis in subjects with normal language function.
Third, this investigation illustrates that use of reference electrodes near active temporal regions such as the ear lobes or mastoid processes distort scalp topographic morphology when scalp FMAER recordings are employed. For example, Figures
11 illustrate the absence of a left temporal response when the common average reference was utilized (Figure
9A). Moreover, the important identification of a missing response was obscured when ear referencing was employed (Figure
11). Thus, typical laboratory use of frontal to mastoid recordings should be avoided. As the investigations demonstrate, use of frontal to ear or mastoid recordings produces a large signal because the two recording electrodes (frontal and mastoid) cross the temporal dipole. However, because both left and right superior temporal gyri contribute to the wide frontal response, a unilaterally missing temporal source is likely to remain undetected. In order to correctly utilize reference free recording techniques, multiple scalp electrodes should be utilized of which at least some should be placed in the sub-temporal regions
Fourth, two patients with developmental dysphasia, both of whom showed absent left sided FMAERs, were selected as examples for this report in order to demonstrate and resolve apparently contradictory findings. One patient (Figure
7) showed surface recordings that suggested an absent left temporal response when, in fact, a left sided source was present upon source analysis yet was aberrant in location and orientation. The second patient also showed an absent left temporal FMAER by surface recording which, however, was validated by source analysis (Figure
5). In certain instances, source analysis appears to be helpful in facilitating the full understanding of FMAER findings. The clinical value of the FMAER remains to be investigated further in comparison to conventional clinical and neurophysiological evaluations of developmental dysphasia.
Fifth, two illustrative cases were provided in order to show that LKS patients may manifest normal, unilaterally abnormal, or bilaterally abnormal FMAERs depending upon the state of severity of their illness. The FMAER may worsen when the illness progresses (Figure
13) and improve when pharmacotherapy is successful (Figure
12). Whether such findings are universal for LKS and/or whether the FMAER shows added value for clinical use with LKS patients remains to be investigated.
Sixth, a small case study of patients with LKS/ESES shows that the FMAER is abnormal only when temporal discharges are present and the primary epileptic source, as identified by source analysis of these discharges, is observed to reside in or near the posterior superior temporal gyrus. Eleven of the 13 abnormal studies demonstrated bilateral abnormality consistent with the Lewine et al. report
 of magnetoencephalogram (MEG) spikes in both superior temporal gyri of LKS patients, and the Takeoka et al. report
 of bilateral volume reduction of these regions in LKS.
The curious lack of isolated right sided FMAER abnormalities may reflect the patient selection criteria, which were based, almost entirely, upon manifest language dysfunction and therefore typically suggestive of left hemisphere dysfunction. Recently, transcranial magnetic stimulation (TMS) studies by Harpaz et al. have demonstrated
 that the right Wernicke’s area seems to be specifically involved in higher language functions. These investigators show data suggesting that this right sided region processes “subordinate meanings” of ambiguous words. For example the word “bank” has a different meaning in association with the words “river” or “teller”. Such subtle language dysfunction may not have brought children in for study or may have been subsumed under the “global decline” diagnosis often reported with early LKS/ESES.
Another question involves how to explain language loss in cases when the FMAER is present (Cases 14–18) and the bilateral Wernicke’s regions are therefore assumed to be functional. An answer may lie in the findings outlined by Newman et al.
 which indicate that the range of cortical areas implicated in speech processing goes well beyond the classical cortical regions typically involved in language. These authors demonstrated that wide frontal areas including Broca’s area and broader inferior temporal regions may be involved in functions typically attributed to Wernicke’s area. Thus generalized as well as focal discharges not involving Wernicke’s areas may be implicated in language deterioration. These questions deserve further study.
Seventh, of two patients with ASD one had a normal FMAER (Figure
15A) and the other was missing a left temporal response (Figure
15B). Although apparently equally language impaired, the patient with the normal FMAER showed clinical evidence of some receptive language competence (Figure
15A), incorporating phonemes into his babbling whereas the other showed no clinical evidence of even such rudimentary receptive language competence (Figure
15B). Of note, Saygin
 demonstrated in adult aphasic patients that lesions involving Wernicke’s area and the superior temporal gyrus predicted deficits in processing of both non-verbal as well as verbal sounds. The value of the FMAER in autism remains to be evaluated further.
On the basis of outlining the technical refinements necessary for successful FMAER administration and analysis and the demonstration of consistent FMAER source localization, the information presented suggests that the FMAER may constitute a sensitive test for the clinical study of childhood language disorders and, in particular, a probe of function within both left and right posterior superior temporal gyri. The FMAER may well be very helpful in the assessment of the capacity of bilateral posterior superior temporal auditory cortex to process frequency modulated signals, a very basic component of spoken human language. Whether the FMAER will be shown to provide added value to currently available laboratory tests and clinical expertise remains to be demonstrated. Detailed studies to detect and assess the FMAER’s potential value in both outpatient clinics and inpatient services are indicated.
In the same sense that the MRI is successfully employed by many clinicians with no detailed knowledge of underlying MRI physics, it is certainly possible for clinicians to successfully employ the FMAER without a full understanding of the role of FM in language. It is only necessary to understand that the FMAER constitutes a probe of the bilateral posterior-temporal language regions and does not assess language function outside of these areas. The FMAER is not yet ‘diagnostic’ for any known disease. Clinicians wishing to employ the technique must know that for scalp recordings a full head of electrodes, including subtemporal electrodes, is best and that evaluation should be done on the common average or Laplacian references, avoiding ear/mastoid references. The clinician should know that the FMAER may be bilaterally or unilaterally normal, absent, or more rarely distorted. The need to supplement studies with source analysis is likely to be infrequent but this technique may sometimes prove helpful.
Invasively, cortical FMAER may assist in the elucidation of language eloquent cortex although the FMAER-negative grid contacts cannot be assumed to have no language function as the FM component of language – although important and widespread– is by no means a constituent of every aspect of hierarchical language processing.
Subsequent investigations will be required to delineate the spectrum of clinical FMAER indications beyond, LKS and invasive surgery, in children as described herein.